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MedWorm: Acute Leukemia provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Acute Leukemia category.

Last Build Date: Tue, 29 Mar 2016 16:50:45 +0100


CXCL12 promotes glycolytic reprogramming in acute myeloid leukemia cells via the CXCR4/mTOR axis

Mon, 28 Mar 2016 22:00:00 +0100

CXCL12 promotes glycolytic reprogramming in acute myeloid leukemia cells via the CXCR4/mTOR axis Leukemia advance online publication, March 29 2016. doi:10.1038/leu.2016.58 Authors: M Braun, M Qorraj, M Büttner, F A Klein, D Saul, M Aigner, W Huber, A Mackensen, R Jitschin & D Mougiakakos (Source: Leukemia)

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Neuropathy correlated with imbalanced Foxp3/IL-17 in bone marrow microenvironment of patients with acute myeloid leukemia.

Mon, 28 Mar 2016 17:23:02 +0100

Authors: Chen C, Liu Y, Hua M, Li X, Ji C, Ma D Abstract Bone marrow (BM) neural tissues are important components of bone marrow microenvironment and play important roles in normal hematopoiesis. Neuropathy of BM can cause immunological alteration in hematopoietic microenvironment. It also can induce the impairment of normal hematopoiesis and promote the development of hematologic diseases. In the present study, we determined the expression levels and clinical significances of nerve-related molecules [nestin, tyrosine hydroxylase (TH), Glial Fibrillary Acidic protein (GFAP) and S100B] and T helper-related molecules (IL-17, Foxp3) in BM of AML patients and controls by immunohistochemical analysis and RT-PCR. Our results showed that the positive rates and expression levels of nestin,...

Nutritional assessment as predictor of complications after hematopoietic stem cell transplantation

Mon, 28 Mar 2016 14:30:05 +0100

Conclusions: After hematopoietic stem cell transplantation, high catabolism was associated with longer length of hospital stay, the need of total parenteral nutrition and platelet and neutrophil engraftment times. Nutritional parameters were not associated with overall survival. (Source: Revista Brasileira de Hematologia e Hemoterapia)

Guidelines on the treatment of acute myeloid leukemia: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular

Mon, 28 Mar 2016 14:30:05 +0100

This report is a review of the most relevant contributions of nonconventional magnetic resonance techniques to the imaging diagnosis of primary central nervous system lymphoma, the differential diagnosis of this disease, and the prognosis of patients. This paper aims to describe a wide range of presentations of primary central nervous system lymphoma, their appearance in imaging, and the differential diagnoses of this disease. (Source: Revista Brasileira de Hematologia e Hemoterapia)

The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes

Sun, 27 Mar 2016 22:00:00 +0100

Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0–17) de novo acute myeloid leukaemia (AML) patients revealed aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement (29%), normal karyotype (15%), RUNX1‐RUNX1T1 (10%), deletions of 5q, 7q and/or 17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML‐RARA (7%) and CBFB‐MYH11 (5%). Single nucleotide polymorphism array (SNP‐A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed ≥1 aberration in 89%; when adding cytogenetic data, this frequency increased to 98%. Uniparental isodisomies (UPIDs) were detected in 13% and copy number aberrations (CNAs) in 63% (median 2/case); three UPIDs and 22 CN...

Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single‐centre cohort study

Sun, 27 Mar 2016 22:00:00 +0100

Summary Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single‐centre, retrospective cohort study on 346 ALL paediatric patients (1–16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0–6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in surviv...

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Role of vitamin D receptor gene polymorphisms in aplastic anemia: a case–control study from China

Sun, 27 Mar 2016 22:00:00 +0100

ConclusionsVDR polymorphisms may contribute to susceptibility to AA and influence the severity and prognosis of AA in a Chinese population. (Source: Clinical and Laboratory Haematology)

Targeting the mTOR Pathway in Leukemia

Sun, 27 Mar 2016 22:00:00 +0100

This article is protected by copyright. All rights reserved (Source: Journal of Cellular Biochemistry)

Significance of a positive Clostridium difficile toxin test after hematopoietic stem cell transplantation

Sun, 27 Mar 2016 22:00:00 +0100

In conclusion, although CDI may be overdiagnosed in HSCT recipients, it is difficult to clinically distinguish between CDI and CD colonization. This article is protected by copyright. All rights reserved. (Source: Clinical Transplantation)

Long‐term follow‐up of patients with acute myeloid leukemia surviving and free of disease recurrence for at least 2 years after autologous stem cell transplantation: A report from the acute leukemia working party of the European Society for Blood and Marrow Transplantation

Sun, 27 Mar 2016 22:00:00 +0100

CONCLUSIONSThe results of the current analysis indicate that late recurrences remain a major concern after autologous stem cell transplantation among patients with AML, indicating the need for close monitoring of minimal residual disease and additional leukemic control measures after transplantation. Cancer 2016. © 2016 American Cancer Society. (Source: Cancer)

Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia

Sun, 27 Mar 2016 22:00:00 +0100

Abstract Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004–2010 we...

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Dietary Intake and Childhood Leukemia: The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) Cohort Study

Sun, 27 Mar 2016 22:00:00 +0100

We present the demographics and nutrient intake at study entry of a prospective cohort evaluating dietary intake in children diagnosed with ALL. (Source: Nutrition)

Bcl6 modulation of acute lymphoblastic leukemia response to chemotherapy.

Sun, 27 Mar 2016 05:28:02 +0100

This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to che...

MiR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1.

Sun, 27 Mar 2016 05:28:02 +0100

In this study, we detected relatively lower expression levels of miR-424&27a in TRAIL-resistant and semi-resistant AML cell lines as well as newly diagnosed patient samples. Overexpression of miR-424&27a, by targeting the 3'UTR of PLAG1, enhanced TRAIL sensitivity in AML cells. Correspondingly, knockdown of PLAG1 sensitized AML cells to TRAIL-induced apoptosis and proliferation inhibition. We further found that PLAG1 as a transcription factor could reinforce Bcl2 promoter activity, causing its upregulation at the mRNA level. Both downregulated PLAG1 and elevated expression of miR-424&27a led to Bcl2 downregulation and augmented cleavage of Caspase8, Caspase3 and PARP in the presence of TRAIL. Restoration of Bcl2 could eliminate their effects on AML TRAIL sensitization. Overall,...

Immunotherapy approaches to treat adult acute lymphoblastic leukemia.

Sat, 26 Mar 2016 18:56:02 +0100

Authors: Maino E, Bonifacio M, Scattolin AM, Bassan R Abstract Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment stand...

Vaginal Stenosis After Gonadotropin-Releasing Hormone Agonist Therapy During Treatment for Acute Lymphoblastic Leukemia

Sat, 26 Mar 2016 08:13:16 +0100

Abstract: A 26-year-old patient with a history of chemotherapy for acute lymphoblastic leukemia presented with secondary amenorrhea and cyclic abdominal pain, and she was found to have vaginal stenosis due to adhesion of vaginal wall. The cause of the adhesion was considered to be vaginal inflammation induced by anticancer agents themselves. It was also considered that poor estrogenization of vaginal mucosa as a result of gonadotropin-releasing hormone agonist therapy, conducted for ovarian protection during chemotherapy, might have exacerbated it. Because it is more likely than ever for us to encounter patients who will undertake or had undertaken chemotherapy with gonadotropin-releasing hormone agonist therapy, keen observation and proper intervention would be important. (Source: Journal...

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Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome Following Allogeneic Stem Cell Transplant: A Retrospective Review

Fri, 25 Mar 2016 23:00:00 +0100

Allogeneic stem cell transplant (allo-SCT) is a potentially curative treatment for high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplant intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High intensity chemotherapy and less aggressive therapy with hypomethylating agents (HA) with and without DLI are often used for post allo-SCT relapse. (Source: Biology of Blood and Marrow Transplantation)

Blastic plasmacytoid dendritic cell neoplasm: From the origin of the cell to targeted therapies; Review

Fri, 25 Mar 2016 23:00:00 +0100

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplant may improve survival. (Source: Biology of Blood and Marrow Transplantation)

Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia.

Fri, 25 Mar 2016 17:33:04 +0100

Authors: Chen L, Sun Y, Wang J, Jiang H, Muntean AG Abstract MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs. RNA-sequencing and pathway analysis identified the c-Myc transcriptional program as one of the top distinguishing features. c-Myc protein levels were highly correlative with AML disease latency in mice. Functionally, overexpression of c-Myc resulted in a ...

Significance of CD99 expression in T-lineage acute lymphoblastic leukemia.

Fri, 25 Mar 2016 15:40:03 +0100

CONCLUSION: CD99 could be used to complement current strategy relying on TdT for diagnosis and monitoring of minimal residual disease during the post-therapy follow up of T-ALL patients. Further studies are needed to confirm these findings. PMID: 27002769 [PubMed - as supplied by publisher] (Source: Cancer Biomarkers)

Beclin-1 and hypoxia-inducible factor-1α genes expression: Potential biomarkers in acute leukemia patients.

Fri, 25 Mar 2016 15:40:03 +0100

CONCLUSIONS: Both Beclin-1 and HIF-1α could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia. PMID: 27002764 [PubMed - as supplied by publisher] (Source: Cancer Biomarkers)

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[Report] Activation of proto-oncogenes by disruption of chromosome neighborhoods

Thu, 24 Mar 2016 23:00:00 +0100

Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecti...

Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia

Thu, 24 Mar 2016 23:00:00 +0100

Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia Leukemia advance online publication, March 25 2016. doi:10.1038/leu.2016.46 Authors: Y Zhou, M Othus, D Araki, B L Wood, J P Radich, A B Halpern, M Mielcarek, E H Estey, F R Appelbaum & R B Walter (Source: Leukemia)

LG-362B targets PML-RARα and blocks ATRA resistance of acute promyelocytic leukemia

Thu, 24 Mar 2016 23:00:00 +0100

LG-362B targets PML-RARα and blocks ATRA resistance of acute promyelocytic leukemia Leukemia advance online publication, March 25 2016. doi:10.1038/leu.2016.50 Authors: X Wang, Q Lin, F Lv, N Liu, Y Xu, M Liu, Y Chen & Z Yi (Source: Leukemia)

Close Correlation of Copy Number Aberrations Detected by Next‐Generation Sequencing with Results from Routine Cytogenetics in Acute Myeloid Leukemia

Thu, 24 Mar 2016 23:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: Genes, Chromosomes and Cancer)

Novel Approaches for the Interim Management of Relapsed/Refractory Acute Lymphocytic Leukemia: Introduction.

Thu, 24 Mar 2016 12:15:01 +0100

Authors: Wang ES PMID: 27007406 [PubMed - as supplied by publisher] (Source: Clinical Advances in Hematology and Oncology)

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Successful Treatment of Invasive Pulmonary Mucormycosis in an Immunocompromised Patient.

Thu, 24 Mar 2016 10:32:02 +0100

Authors: Afolayan O, Copeland H, Hargrove R, Zaheer S, Wallen JM Abstract A 59-year-old man undergoing chemotherapy for acute myelogenous leukemia had a bilateral pneumonic process. The right lung subsequently developed several small cavitary lesions extending from the central hilum to the chest wall. Despite medical therapy, repeat imaging demonstrated coalescence into a single, large, central cavitary lesion. Thoracic surgery was consulted because of the central hilar involvement of all three lobes; a pneumonectomy would have been required to resect the lesion. However, he was not a candidate for pneumonectomy because of a low predicted postoperative forced expiratory volume in 1 second. We performed a rib resection, debridement, and marsupialization, in which the skin was sewn ...

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

Thu, 24 Mar 2016 05:43:33 +0100

Abstract Many B‐cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK‐92 cells, a continuously growing NK cell line, showing that anti‐CD19‐CAR (αCD19‐CAR) engineered NK‐92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK‐92 cells. The ‘first generation’ CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3ζ chain and a Myc‐tag and cloned into a retrovir...

PAX5 promotes pre-B cell proliferation by regulating the expression of pre-B cell receptor and its downstream signaling

Wed, 23 Mar 2016 23:00:00 +0100

Publication date: May 2016 Source:Molecular Immunology, Volume 73 Author(s): Kai Xue, Jiazhe Song, Yan Yang, Zhi Li, Chunhua Wu, Jinhua Jin, Wenzhe Li PAX5 is indispensable for the commitment of early lymphoid progenitors to the B cell lineage as well as for the development of B cells. Although previous studies have indicated that the Pax5-conditional-knockout mouse exhibited dedifferentiation of mature B cell and the development of aggressive lymphomas, the changes of Pax5 gene expressions in pre-B cells have not been analyzed. To understand the functional importance of Pax5 gene in the proliferation and survival of pre-B cells, we established a Pax5-knockdown model using 70Z/3 pre-B cell line. Pax5 knockdown 70Z/3 cells (70Z/3-KD cells) showed down-regulations of pre-BCR compoun...

Myeloid Sarcoma of the Hepatobiliary System: A Case Series and Review of the Literature.

Wed, 23 Mar 2016 23:00:00 +0100

Authors: Norsworthy KJ, Bhatnagar B, Singh ZN, Gojo I Abstract Myeloid sarcoma (MS) is a rare extramedullary presentation of myeloid malignancies, most commonly seen in association with acute myeloid leukemia (AML). Although MS can develop in any organ, the involvement of the hepatobiliary system is rare. With clinical manifestations of jaundice, abdominal pain and other gastrointestinal symptoms, MS presenting at this location can be a challenge to diagnose, particularly in patients with no known history of hematologic malignancy. This may cause delay in proper management. Here we report 3 cases from a single institution and a review of the literature concerning the epidemiology, clinical presentation, treatment and outcomes in patients with MS of the liver, biliary tree and pancr...

Hypomethylating Agents for Relapse after Allogeneic Hematopoietic Cell Transplantation in Myeloid Malignancies: A Case Series and Review of the Literature.

Wed, 23 Mar 2016 23:00:00 +0100

CONCLUSION: HMAs for relapse after HCT can be effective in inducing a CR. This may be due to epigenetic changes and immunomodulatory effects that enhance the graft-versus-leukemia effect. There may be a risk of GVHD, and further exploration into pathophysiology and predisposing factors are warranted. PMID: 27007668 [PubMed - as supplied by publisher] (Source: Acta Haematologica)

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Acute pulmonary edema with new giant V wave immediately after pericardiocentesis

Wed, 23 Mar 2016 23:00:00 +0100

A 42-year-old Japanese man was diagnosed as having acute lymphoblastic leukemia and received multi-agent chemotherapy, including doxorubicin, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in March 2014. As he failed to achieve complete remission, he was admitted to our hospital to undergo repeat allo-HSCT in March 2015. He had no history of cardiovascular disease or hypertension. Echocardiography showed normal left ventricular (LV) function with no pericardial effusion before repeat allo-HSCT (Fig. (Source: International Journal of Cardiology)

Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups

Wed, 23 Mar 2016 23:00:00 +0100

The initial report of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m2) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or a FLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m2), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P = .001). Young...

Increased DNA methylation of Dnmt3b targets impairs leukemogenesis

Wed, 23 Mar 2016 23:00:00 +0100

The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells. Dnmt3b has recently been shown to play a role in genic methylation. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knock-in mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function. Forced Dnmt3b expression induced widespread DNA hypermethylation in Myc-Bcl2–induced leukemias, preferentially at gene bodies. MLL-AF9–induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was ...

Acute Lymphoblastic Leukemia Transformation in Polycythemia Vera: A Rare Phenomenon

Wed, 23 Mar 2016 23:00:00 +0100

Abstract Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. ...

Relationhip between event-free survival and overall survival in acute myeloid leukemia: A report from SWOG, HOVN/SAKK, and MRC/NCRI.

Wed, 23 Mar 2016 23:00:00 +0100

Authors: Othus M, van Putten W, Lowenberg B, Petersdorf SH, Nand S, Erba H, Appelbaum F, Hills R, Russell N, Burnett A, Estey E PMID: 27013652 [PubMed - as supplied by publisher] (Source: Haematologica)

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Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome.

Wed, 23 Mar 2016 23:00:00 +0100

In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naive cells). PMID: 27013649 [PubMed - as supplied by publisher] (Source: Haematologica)

Hypomethylating Agents for Relapse after Allogeneic Hematopoietic Cell Transplantation in Myeloid Malignancies: A Case Series and Review of the Literature

Wed, 23 Mar 2016 21:26:23 +0100

Conclusion: HMAs for relapse after HCT can be effective in inducing a CR. This may be due to epigenetic changes and immunomodulatory effects that enhance the graft-versus-leukemia effect. There may be a risk of GVHD, and further exploration into pathophysiology and predisposing factors are warranted.Acta Haematol 2016;135:232-237 (Source: Acta Haematologica)

Myeloid Sarcoma of the Hepatobiliary System: A Case Series and Review of the Literature

Wed, 23 Mar 2016 21:26:23 +0100

Myeloid sarcoma (MS) is a rare extramedullary presentation of myeloid malignancies, most commonly seen in association with acute myeloid leukemia (AML). Although MS can develop in any organ, the involvement of the hepatobiliary system is rare. With clinical manifestations of jaundice, abdominal pain and other gastrointestinal symptoms, MS presenting at this location can be a challenge to diagnose, particularly in patients with no known history of hematologic malignancy. This may cause delay in proper management. Here we report 3 cases from a single institution and a review of the literature concerning the epidemiology, clinical presentation, treatment and outcomes in patients with MS of the liver, biliary tree and pancreas.Acta Haematol 2016;135:241-251 (Source: Acta Haematologica)

Rapid Capture Next‐Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B‐Cell Precursor ALL

Wed, 23 Mar 2016 19:08:02 +0100

Comprehensive next‐generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph‐like B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high‐risk BCP‐ALL, we developed a PCR‐independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5′ fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrich...

Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells

Wed, 23 Mar 2016 16:34:15 +0100

Conclusions: The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy.Cell Physiol Biochem 2016;38:1288-1302 (Source: Cellular Physiology and Biochemistry)

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The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

Wed, 23 Mar 2016 07:43:49 +0100

We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE. (Source: Genetics and Molecular Biology)

Bilateral Aleukemic Myeloid Sarcoma of the Eyelids With Indolent Course

Wed, 23 Mar 2016 04:43:42 +0100

Abstract: Leukemic infiltrates may be seen in the skin in the absence of detectable bone marrow involvement. Leukemia cutis may exceptionally occupy the eyelids. An unusual case of a 58-year-old man presenting bilateral erythematous eyelid lesions, proven to be aleukemic leukemia cutis, is reported. Biopsy was conducted and hematoxylin/eosin stained sections were histologically evaluated. Immunohistochemistry was also performed. Light microscopy revealed cutaneous infiltration by a neoplastic population consisting of medium-sized cells. These cells infiltrated the overlying epidermis leading to focal microulcerations. The morphological and immunohistochemical characteristics of the neoplastic population were compatible with myeloid leukemia cutis. The bone marrow biopsy was normocellular ...

Leukemic optic nerve infiltration in a patient with acute lymphoblastic leukemia

Wed, 23 Mar 2016 04:26:49 +0100

Conclusion: Isolated optic nerve relapse of leukemic infiltration is of paramount importance to early diagnosis, as vision can be saved if treatment is initiated promptly. (Source: Retinal Cases and Brief Reports)

Outcome of children and adolescents with lymphoblastic lymphoma

Wed, 23 Mar 2016 03:16:17 +0100

Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.RESUMO Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados...

The Effects of Arsenic Trioxide in Combination with Retinoic Acids on Cutaneous T-Cell Lymphoma Cell Lines

Wed, 23 Mar 2016 01:22:59 +0100

Cutaneous T-cell lymphomas (CTCL) are characterized by an infiltration of the skin with malignant T cells. Curative treatments for aggressive entities such as Sézary syndrome have not been identified yet. Arsenic trioxide (AsO3) is used for the treatment of acute promyelocytic leukemia in combination with retinoids. As the latter are established treatment options in CTCL, we sought to evaluate the efficacy of AsO3 for mono- and combination therapy in vitro. Analyses for apoptosis, cell cycle inhibition, cytotoxicity and cell viability were made after incubation of CTCL cells with AsO3 alone or in combination with the retinoids all-trans-retinoic acid or bexarotene. While AsO3 induced apoptosis, retinoids did not at the time point of analysis. However, retinoids strongly reduced cell viabi...

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Development of ZMYM2‐FGFR1 driven AML in human CD34+ cells in immunocompromised mice

Tue, 22 Mar 2016 23:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: International Journal of Cancer)

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study [Hematologic Malignancy]

Tue, 22 Mar 2016 23:00:00 +0100

Conclusion In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 μg/m2/day. Single-agent blinatumomab showed antilymphoma activity. (Source: Journal of Clinical Oncology)

Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease [Hematologic Malignancy]

Tue, 22 Mar 2016 23:00:00 +0100

Conclusion Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. (Source: Journal of Clinical Oncology)

Evolutionary Dynamics of Chronic Myeloid Leukemia Progression: the Progression-Inhibitory Effect of Imatinib

Tue, 22 Mar 2016 23:00:00 +0100

Abstract The t(9;22) translocation that causes chronic myeloid leukemia (CML) drives both transformation and the progression process that eventually results in the disease changing to acute leukemia. Constitutively activated Bcr-Abl signaling in CML creates high levels of reactive oxygen species (ROS) that produce 8-oxo-guanine in DNA; this is mutagenic and causes chronic phase (CP) progression to blast phase (BP). We modeled three types of mutations involved in this progression: mutations that result in myeloid progenitor cells proliferating independently of external growth factors; mutations causing failure of myeloid progenitor cells to differentiate; and mutations that enable these cells to survive independently of attachment to marrow stroma. We further modeled tyrosine kinas...

Reduction in Cell Viability and in Homeobox Protein Levels Following in Vitro Exposure to δ-tocopherol in Acute Myeloid Leukemia.

Tue, 22 Mar 2016 23:00:00 +0100

In this study, we screened the efficacy of δ-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS-associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of δ-T as low as 20 µM. The antileukemic activity of δ-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of δ-T against KG-1 cells. The mechanism of cell growth inhibition of δ-T was through downregulation of cy...

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Significance of BAFF/APRIL Expression and Their Receptors in Pediatric Patients With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescen...

Strategies to Prevent and Manage Thrombotic Complications of Acute Lymphoblastic Leukemia in Children and Young People Vary Between Centers in the United Kingdom

Tue, 22 Mar 2016 07:43:43 +0100

There is a lack of evidence-based guidance for the prevention and management of thrombosis in children and young people treated for acute lymphoblastic leukemia. To determine current UK practice, a survey was sent to 28 centers participating in the Medical Research Council UKALL 2011 trial. Marked variation in practice was noted. In total, 43% of centers defer central venous access device insertion until end of induction for treatment of low-risk disease. Central venous access devices are removed at the end of intensive blocks in 38% and end of treatment in 42%. Duration of anticoagulation for line-associated thrombosis is 6 weeks in 43% and 3 months in 33% and for cerebral sinovenous thrombosis is 3 months in 71% and 6 months in 24%. Platelet transfusion to maintain platelet count >50×10...

Multimodality Imaging in Pediatric Osteosarcoma in the Era of Image Gently and Image Wisely Campaign With a Close Look at the CT Scan Radiation Dose

Tue, 22 Mar 2016 07:43:43 +0100

This study reviews the utilization of multimodality imaging in patients with osteosarcoma at our institution and analyzes any potential radiation-related complications. Twenty-eight patients were identified. Three patients developed late complications—acute myeloid leukemia, myelodysplastic syndrome, and early menopause. Using the patient’s age and body part imaged, CT dose length product and effective dose was estimated with the use of a conversion factor for 19 patients. The effective doses were higher in the 3 patients with late complications than the other patients in the cohort (P=0.018). These results suggest an increased risk for adverse effects with higher CT exposures and effective doses. On the basis of our data and published data, methods to decrease the doses of radiation f...

Severe Hypercalcemia in a Child With Acute Lymphoblastic Leukemia Relapse: Successful Management With Combination of Calcitonin and Bisphosphonate

Tue, 22 Mar 2016 07:43:43 +0100

In conclusion, because of the postponed effect of bisphosphonate treatment, pamidronate and calcitonin combination is an effective treatment option in the early resolution of malignancy-related hypercalcemia. (Source: Journal of Pediatric Hematology Oncology)

Sorafenib-induced Posterior Reversible Encephalopathy Syndrome in a Child With FLT3-ITD-positive Acute Myeloid Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

Conclusions: Thus, PRES might be a rare, potentially serious, but manageable, side effect of sorafenib that should be kept in mind by pediatric hematologists and oncologists. (Source: Journal of Pediatric Hematology Oncology)

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Early-onset SMART Syndrome in an 11-Year-old Child With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

No abstract available (Source: Journal of Pediatric Hematology Oncology)

Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

The purpose of the study was to assess the risk of first-time bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL treated at 3 pediatric centers in Denmark between 2008 and 2014. A total of 136 patients were followed from initial CVC placement until first BSI, CVC removal, death, or day 28, whichever occurred first. Thirty-nine BSIs were detected, of which 67% were gram-positive infections, and 59% met the criteria for being CVC associated. The 28-day cumulative incidence of BSI was similar in 77 patients with a nontunneled CVC (28%; 95% confidence interval, 19%-40%) and in 59 patients with a tunneled CVC with...

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

Conclusions: RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings. (Source: Journal of Pediatric Hematology Oncology)

Id: 36: pegaspargase induced severe pancreatitis. friend or foe?

Mon, 21 Mar 2016 23:00:00 +0100

We report a case to increase the awareness of higher incidence of pegaspargase-induced pancreatitis, which is a rare but potentially deadly complication. Clinicians should monitor triglycerides while on treatment and suspect pancreatitis if patient develops abdominal pain. If pancreatitis occurs, therapy should be stopped and not reinstituted. For patients with hypertriglyceridemia without pancreatitis discontinuation of therapy should be considered. Abstract ID: 36 Figure 1Impression: Severe acute pancreatitis. Significant interval worsening. (Source: Journal of Investigative Medicine)

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Id: 92: ceramide accumulation in mitochondria: a novel therapeutic strategy for acute myeloid leukemia via inducing lethal mitophagy

Mon, 21 Mar 2016 23:00:00 +0100

This study investigates the biological role of ceramide lipid in the response of AML to FLT3 targeted therapy and aims at finding mechanism-based alternative therapeutic strategies to overcome resistance to FLT3 inhibitors. We found that AML cell lines and patient samples expressing FLT3 have suppressed CerS1 expression and lower levels of its product C18-ceramide compared with FLT3 negative AML cells. Silenced FLT3 expression or its pharmacological inhibition increased CerS1 and C18-ceramide levels while FLT3 overexpression suppressed them. The increase in C18-ceramide after FLT3 inhibition is required for cell death as silencing CerS1 expression or inhibiting its enzymatic activity protected from FLT3 inhibitors-induced cell death in vitro and in vivo. Mechanistically, FLT3 inhibition re...

Id: 95: il-33/st2 triggering of il-9-secreting t cells: from proteomics to therapeutics

Mon, 21 Mar 2016 23:00:00 +0100

As one of the most validated immunotherapies to date, allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for high-risk hematological malignancies, particularly acute myeloid leukemia (AML). The immunotherapeutic activity of allo-HCT is known as the graft-vs-leukemia (GVL) activity. However, GVL activity is often accompanied by T-cell reactivity to allo-antigens in normal host tissues, which leads to graft-versus-host disease (GVHD), another major cause of death after HCT. Therefore, there is a great unmet need to improve the current process of allo-HCT through increasing the GVL activity and decreasing GVHD. We have shown that an elevated plasma level of soluble (s)ST2 in HCT patients is a risk factor for severe GVHD. ST2 blockade reduces sST2-produci...

The NEDD8-activating enzyme inhibitor MLN4924 induces G2 arrest and apoptosis in T-cell acute lymphoblastic leukemia.

Mon, 21 Mar 2016 05:47:03 +0100

Authors: Han K, Wang Q, Cao H, Qiu G, Cao J, Li X, Wang J, Shen B, Zhang J Abstract The first-in-class compound MLN4924 is a small molecule inhibitor that selectively inactivates NEDD8-activating enzyme (NAE). The anticancer effects of MLN4924 have been attributed to impaired neddylation of Cullin proteins. Here, we show that treatment of T-cell acute lymphoblastic leukemia (T-ALL) cells with MLN4924 potently suppressed the neddylation of Cullins and the oncogenic growth of T-ALL cells in-vitro. Moreover, MLN4924 induced disease regression in an in vivo xenograft model. MLN4924 also induced cell cycle arrest at G2 phase and apoptosis in T-ALL cells. However, inhibition of the neddylation of Cullins alone could not explain the effects of MLN4924 in T-ALL cells. Gene expression profi...

Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia

Mon, 21 Mar 2016 00:00:00 +0100

Abstract Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were ...

Unique Familial MLL(KMT2A)‐Rearranged Precursor B‐Cell Infant Acute Lymphoblastic Leukemia in Non‐twin Siblings

Mon, 21 Mar 2016 00:00:00 +0100

ConclusionsWhether because of a deleterious transplacental exposure, novel predisposition syndrome, or exceedingly rare chance occurrence, MLL‐R infant ALL can occur in non‐twin siblings. The discordant occurrence of infant ALL in the monozygous twins was likely because they were dichorionic. (Source: Pediatric Blood and Cancer)

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Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?

Mon, 21 Mar 2016 00:00:00 +0100

Summary The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft‐versus‐host disease (c‐GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1‐year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1‐year incidence of c‐GvHD was 20 ± 7% for MC, and 18 ± 4% for CC patients (P = 0·734). The 3‐year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 ...

Leukemia cells display lower levels of intracellular cholesterol irrespective of the exogenous cholesterol availability.

Sun, 20 Mar 2016 23:00:00 +0100

CONCLUSIONS: Present study provides convincing evidence to prove that the cellular free cholesterol and cholesteryl ester content is significantly reduced in leukemia cells in comparison to normal hematopoietic cells in circulation. Moreover, it was shown that the lower levels of cholesterol in leukemia cells are not affected by exogenous cholesterol availability. PMID: 27012514 [PubMed - as supplied by publisher] (Source: International Journal of Clinical Chemistry)

Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia.

Sun, 20 Mar 2016 05:19:02 +0100

This article provides an overview of blinatumomab, its benefits demonstrated in clinical trials, adverse effects, administration details, and the role of the oncology nurse in caring for and educating patients who receive blinatumomab. METHODS: This article summarizes the results of two phase II studies on blinatumomab and provides practice implications for nurses caring for patients receiving this therapy. FINDINGS: Attentive symptom monitoring and management are crucial. Individuals who achieve remission from blinatumomab can then be considered for stem cell transplantation and a chance for cure. PMID: 26991709 [PubMed - in process] (Source: Clinical Journal of Oncology Nursing)

Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection.

Sat, 19 Mar 2016 17:53:03 +0100

Authors: Pérez-Figueroa E, Sánchez-Cuaxospa M, Martínez-Soto KA, Sánchez-Zauco N, Medina-Sansón A, Jiménez-Hernández E, Torres-Nava JR, Félix-Castro JM, Gómez A, Ortega E, Maldonado-Bernal C Abstract Children with acute lymphoblastic leukemia (ALL) often present fever. Febrile states are usually associated with infectious processes that generate an inflammatory response involving various molecules, including cytokines. However, an inflammatory response may also occur in the absence of infection. We hypothesized that the levels of inflammatory cytokines are increased in children with ALL without apparent infection. The serum levels of 13 cytokines in 99 patients with ALL and 48 non-oncological patients without apparent infection were measured using multiplex analyte prof...

Emetine induces chemosensitivity and reduces clonogenicity of acute myeloid leukemia cells.

Sat, 19 Mar 2016 17:51:03 +0100

This study validated the anti-leukemiceffect of emetine in AML cell lines, a group of diverse AML primary samples, and in a human AML-transplanted murine model, sparing healthy blood cells. The selective anti-leukemic effect of emetine together with the safety of the dose range required to exert this effect support the development of this agent in clinical practice. PMID: 26992240 [PubMed - as supplied by publisher] (Source: Oncotarget)

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The Wilms Tumor-1 (WT1) rs16754 polymorphism is a prognostic factor in acute myeloid leukemia (AML): a meta-analysis.

Sat, 19 Mar 2016 17:51:03 +0100

In conclusion, WT1 rs16754 polymorphism is associated with better survival of AML. It could be used as a cost-effective prognostic biomarker for AML. PMID: 26992216 [PubMed - as supplied by publisher] (Source: Oncotarget)

Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen.

Sat, 19 Mar 2016 17:51:03 +0100

Authors: Lynch JT, McEwen R, Crafter C, McDermott U, Garnett MJ, Barry ST, Davies BR Abstract Selective phosphoinositide 3-kinase (PI3K)/AKT/mTOR inhibitors are currently under evaluation in clinical studies. To identify tumor types that are sensitive to PI3K pathway inhibitors we screened compounds targeting PI3Kα/δ (AZD8835), PI3Kβ/δ (AZD8186), AKT (AZD5363) and mTORC1/2 (AZD2014) against a cancer cell line panel (971 cell lines). There was an enrichment of hematological malignancies that were sensitive to AKT and mTOR inhibition, with the greatest degree of sensitivity observed in T-cell acute lymphoblastic leukemia (T-ALL). We found that all NOTCH mutant T-ALL cell lines were sensitive to AKT and mTORC1/2 inhibitors, with only partial sensitivity to agents that target the P...

Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study

Sat, 19 Mar 2016 00:00:00 +0100

We report the results of patients with acute leukaemia (leukaemia cohort). Methods In this dose-escalation, phase 1 study we recruited patients from seven university hospital centres (in France [five], UK [one], and Canada [one]). Adults with acute leukaemia who had failed or had a contraindication to standard therapies were eligible to participate. OTX015 was given orally at increasing doses from 10 mg/day to 160 mg/day (14 of 21 days), using a conventional 3 + 3 design. In this open-label trial, OTX015 was initially administered once a day, with allowance for exploration of other schedules. The primary endpoint was dose-limiting toxicity (DLT), assessed during the first treatment cycle (21 days). The study is ongoing and is registered with, NCT01713582. Finding...

IDH mutations in cancer and progress toward development of targeted therapeutics

Sat, 19 Mar 2016 00:00:00 +0100

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG). IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials. IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of αKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation...

Risk of second primary malignancies among 1537 melanoma patients and risk of second primary melanoma among 52 354 cancer patients in Northern Italy

Fri, 18 Mar 2016 19:20:05 +0100

ConclusionsThe most likely causes of these associations are the clustering of lifestyle risk factors in the same subgroups of population, mainly on a sociocultural basis and surveillance bias. This raises important questions about how to best follow cancer survivors by avoiding an inefficient use of resources and an excessive medicalization of these patients' lives. (Source: Journal of the European Academy of Dermatology and Venereology)

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New compound is effective against drug-resistant leukemia, preclinical study finds

Fri, 18 Mar 2016 16:36:09 +0100

A novel compound MRX-2843 more than doubled the median days of survival in laboratory models with a drug-resistant form of the acute myeloid leukemia, scientists report in a new article. (Source: ScienceDaily Headlines)

Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders.

Fri, 18 Mar 2016 15:37:03 +0100

Authors: Chen H, Liu S, Liu J, Chai C, Mao H, Yu Z, Tang Y, Zhu G, Chen HX, Zhu C, Shao H, Tan S, Wang Q, Bi Y, Zou Z, Liu G, Jin T, Jiang C, Gao GF, Peiris M, Yu H, Chen E Abstract A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-...

Secondary bone marrow malignancies after adjuvant chemotherapy for breast cancer: a report of 2 cases and a review of the literature.

Fri, 18 Mar 2016 12:25:02 +0100

CONCLUSIONS: By literature review, these 2 cases do not support the relationship between primary tumor treatment and secondary cancer, but strongly suggest the need for histologic samples when bone metastasis occurred after years from diagnosis of breast cancer. In this setting, the oncologist should take into account a secondary bone marrow tumor before starting treatment for breast cancer. PMID: 26979247 [PubMed - as supplied by publisher] (Source: Tumori)

Peripapillary retinal leukemic infiltration associated with papilledema in a T-ALL patient without cranial or optic nerve involvement.

Fri, 18 Mar 2016 12:25:02 +0100

CONCLUSIONS: To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema. PMID: 26979244 [PubMed - as supplied by publisher] (Source: Tumori)

South Africa: Durban Youngster Wants to Raise Cancer Awareness

Fri, 18 Mar 2016 09:35:16 +0100

[News24Wire] Twenty-year-old Tashnika Rambali was diagnosed with Acute Lymphoblastic Leukaemia when she was just 18, a diagnosis that threw her future into an uncertain spin. (Source: AllAfrica News: Health and Medicine)

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Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients.

Fri, 18 Mar 2016 05:56:02 +0100

Authors: Soverini S, De Benedittis C, Machova Polakova KM, Linhartova J, Castagnetti F, Gugliotta G, Papayannidis C, Mancini M, Klamova H, Salvucci M, Crugnola M, Iurlo A, Albano F, Russo D, Rosti G, Cavo M, Baccarani M, Martinelli G Abstract In chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients who fail imatinib treatment, BCR-ABL1 mutation profiling by Sanger sequencing (SS) is recommended before changing therapy since detection of specific mutations influences second-generation tyrosine kinase inhibitor (2GTKI) choice. We aimed to assess i) in how many patients who relapse on second-line 2GTKI therapy next generation sequencing (NGS) may track resistant mutations back to the sample collected at the time of imatinib resistan...

Dibenzo[def,p]chrysene transplacental carcinogenesis in wild‐type, Cyp1b1 knockout, and CYP1B1 humanized mice

Fri, 18 Mar 2016 00:34:13 +0100

The cytochrome P450 (CYP) 1 family is active toward numerous environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs). Utilizing a mouse model, null for Cyp1b1 and expressing human CYP1B1, we tested the hypothesis that hCYP1B1 is important for dibenzo[def,p]chrysene (DBC) transplacental carcinogenesis. Wild‐type mCyp1b1, transgenic hCYP1B1 (mCyp1b1 null background), and mCyp1b1 null mice were assessed. Each litter had an equal number of siblings with Ahrb‐1/d and Ahrd/d alleles. Pregnant mice were dosed (gavage) on gestation day 17 with 6.5 or 12 mg/kg of DBC or corn oil. At 10 months of age, mortality, general health, lymphoid disease and lung tumor incidence, and multiplicity were assessed. hCYP1B1 genotype did not impact lung tumor multiplicity, but tended to en...

NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia

Fri, 18 Mar 2016 00:00:00 +0100

Publication date: Available online 17 March 2016 Source:Cell Reports Author(s): Jessica N. Nichol, Matthew D. Galbraith, Claudia L. Kleinman, Joaquín M. Espinosa, Wilson H. Miller Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. I...

MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO

Fri, 18 Mar 2016 00:00:00 +0100

by Nicole Kohrs, Stephan Kolodziej, Olga N. Kuvardina, Julia Herglotz, Jasmin Yillah, Stefanie Herkt, Alexander Piechatzek, Gabriela Salinas Riester, Thomas Lingner, Christian Wichmann, Halvard Bonig, Erhard Seifried, Uwe Platzbecker, Hind Medyouf, Manuel Grez, Jörn Lausen A network of lineage-specific transcription factors and microRNAs tightly regulates differentiation of hematopoietic stem cells along the distinct lineages. Deregulation of this regulatory network contributes to impaired lineage fidelity and leukemogenesis. We found that the hematopoietic master regulator RUNX1 controls the expression of certain microRNAs, of importance during erythroid/megakaryocytic differentiation. In particular, we show that the erythorid miR144/451 cluster is epigenetically repressed by RUNX1 duri...

A Study of Human Leukocyte Antigen Mismatched Cellular Therapy (Stem Cell Microtransplantation) in High-Risk Myelodysplastic Syndrome or Transformed Acute Myelogenous Leukemia

Fri, 18 Mar 2016 00:00:00 +0100

The treatment outcomes of myelodysplastic syndrome (MDS) and transformed acute myelogenous leukemia (tAML) remain very unsatisfactory. We designed a combination of human leukocyte antigen (HLA)-mismatched hematopoietic stem cell microtransplantation (MST) with chemotherapy for patients with MDS and tAML and evaluated its effects and toxicity. Patients were between 13 and 79 years old. Patients with MDS (n = 21) were given HLA-mismatched MST combined with decitabine and cytarabine; patients with tAML (n = 22) were given HLA-mismatched MST combined with decitabine and cytarabine, and also mitoxantrone. Patients in complete remission (CR) also received MST plus decitabine and medium-dose cytarabine chemotherapy without graft-versus-host disease (GVHD) prophylaxis. The overall response rate of...

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Mutations of TP53 in adult acute lymphoblastic leukemia at diagnosis do not affect the achievement of hematologic response but correlate with early relapse and very poor survival.

Fri, 18 Mar 2016 00:00:00 +0100

Authors: Salmoiraghi S, Guinea Montalvo ML, Ubiali G, Tosi M, Peruta B, Zanghi' P, Oldani E, Boschini C, Kohlmann A, Bungaro S, Intermesoli T, Terruzzi E, Angelucci E, Cavattoni I, Ciceri F, Bassan R, Rambaldi A, Spinelli O PMID: 26992948 [PubMed - as supplied by publisher] (Source: Haematologica)

Myelodysplastic Syndrome and Acute Lymphocytic Leukemia in Common Variable Immunodeficiency (CVID)

Thu, 17 Mar 2016 23:00:00 +0100

(Source: Journal of Clinical Immunology)

Clinical value to quantitate hematogones in Chinese childhood acute lymphoblastic leukemia by flow cytometry analysis

Thu, 17 Mar 2016 08:34:18 +0100

ConclusionThe strong independently prognostic impact indicated that the better HGs regeneration is a marker of better response to therapy. (Source: Clinical and Laboratory Haematology)

Identification of a novel tyrosine kinase inhibitor for acute myeloid leukemia

Thu, 17 Mar 2016 04:00:00 +0100

(Journal of Clinical Investigation) A new study in JCI Insight reports the development of a new drug that targets both resistant tumors and FLT3-independent acute myeloid leukemia. (Source: EurekAlert! - Cancer)

SON and Its Alternatively Spliced Isoforms Control MLL Complex-Mediated H3K4me3 and Transcription of Leukemia-Associated Genes

Thu, 17 Mar 2016 00:00:00 +0100

Kim et al. demonstrate that SON and its splice variants control MLL complex-mediated transcriptional initiation. Full-length SON binds menin and inhibits MLL complex assembly, decreasing H3K4me3. Short, alternatively spliced SON isoforms are upregulated in acute myeloid leukemia and antagonize full-length SON function. (Source: Molecular Cell)

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Pharmacokinetics of high-dose methotrexate in infants aged less than 12 months treated for aggressive brain tumors

Thu, 17 Mar 2016 00:00:00 +0100

Conclusions Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg. (Source: Cancer Chemotherapy and Pharmacology)

Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge

Thu, 17 Mar 2016 00:00:00 +0100

Girish V Badarkhe, Amrita Sil, Sabari Bhattacharya, Uttam Kumar Nath, Nilay Kanti DasIndian Journal of Pharmacology 2016 48(2):216-218Erythema multiforme (EM) is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO) lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as “probable.” The rash responded to topical corticosteroids and antih...

Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

Thu, 17 Mar 2016 00:00:00 +0100

In this study, we generate a Gata2Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. We show that all the HSCs are Gata2 expressing. However, not all HPCs in the aorta, vitelline and umbilical arteries, and fetal liver require or express Gata2. These Gata2-independent HPCs exhibit a different functional output and genetic program, including Ras and cyclic AMP response element-binding protein pathways and other Gata factors, compared with Gata2-dependent HPCs. Our results, indicating that Gata2 is of major importance in programming toward HSC fate but not in all cells with HPC fate, have implications for current reprogramming strategies. (Source: Blood)

Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia

Thu, 17 Mar 2016 00:00:00 +0100

Patients with relapsed acute myeloid leukemia (AML) have limited therapeutic options. Vesicular stomatitis virus (VSV)–interferon β (IFNβ)–sodium iodide symporter (NIS) is an oncolytic VSV encoding IFNβ and the NIS reporter. Syngeneic AML C1498 tumors responded to IV therapy with VSV-murine IFNβ (mIFNβ)-NIS in a dose-dependent manner. Imaging for NIS expression showed robust virus infection within the tumors. Virus infection did not increase programmed death ligand 1 (PD-L1) on tumor cells. Combining VSV-mIFNβ-NIS with anti-PD-L1 antibody (Ab) therapy enhanced antitumor activity compared with treatment with virus alone or Ab alone; this enhancement was not significant at higher VSV-mIFNβ-NIS doses. Systemic VSV therapy reduced systemic C1498&n...

Novel TNF-related Apoptotic-inducing Ligand-based Immunotoxin for Therapeutic Targeting of CD25 Positive Leukemia

Wed, 16 Mar 2016 23:00:00 +0100

Abstract Background Human TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia. Aim Our aim was to develop an immunotoxin to target CD25+ leukemic cells. Methods Recombinant fusion construct comprising human IL2α and TRAIL114–281 was cloned, expressed an...

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Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults

Wed, 16 Mar 2016 23:00:00 +0100

Abstract The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improve...

Cancer incidence in France over the 1980-2012 period: Hematological malignancies.

Wed, 16 Mar 2016 14:18:02 +0100

CONCLUSION: The striking differences in the incidence patterns by histologic subtype strongly suggest a certain level of etiologic heterogeneity among hematological malignancies and support the pursuit of epidemiologic analysis by subtype for HMs in international studies. Age-standardized incidence rates are essential to analyze trends in risk, whereas the number of incident cases is necessary to make provisions for healthcare resources and to evaluate the overall burden of HM. PMID: 26973179 [PubMed - as supplied by publisher] (Source: Revue d Epidemiologie et de Sante Publique)

Cellular protein plays important role in aggressive childhood cancer

Wed, 16 Mar 2016 04:07:58 +0100

UCLA scientists have uncovered how a cellular protein contributes to an aggressive form of leukemia prevalent in young children. The discovery is an important step forward in the effort to better understand and treat aggressive childhood leukemia. The study was published in the Journal of Clinical Investigation. “Certain subtypes of leukemia are very hard to treat and typically children with these subtypes have poor prognosis,” said Dr. Dinesh Rao, the study’s senior author and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “Pinpointing specific differences in how cancer cells function is critical in the development of targeted treatments, especially for these types of aggressive cancers that often recur and don’t respond well to...

An e13a3 BCR‐ABL1 fusion transcript in variant t(9;22;17)(q34;q11;q21)‐positive adult acute lymphoblastic leukemia

Wed, 16 Mar 2016 00:00:00 +0100

(Source: Clinical and Laboratory Haematology)