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MedWorm: Leukemia



MedWorm.com 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 Leukemia category.



Last Build Date: Tue, 29 Mar 2016 16:48:00 +0100

 



Antibiotic resistance pattern of HA-MRSA strains isolated from leukemia patients in Baghdad, Iraq

Tue, 29 Mar 2016 09:23:39 +0100

Background: Staphylococcus aureus (S. aureus) is an important pathogen for hospital-associated infections, and it is especially difficult to treat because of emerging resistance to many antimicrobial drugs. Methicillin-resistant S. aureus (MRSA) have emerged as a clinically relevant human pathogen. Intracellular destruction of invading S. aureus is mainly mediated by phagocytosis, and this phagocytic process is crucial to the host innate defense against Staphylococci, so, disorders of phagocytic cells- as in cases of leukemia- cause frequency of infections at epithelial surfaces and the frequency of dissemination. (Source: International Journal of Infectious Diseases)

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EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways

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

Hongyu Li, Manmei Li, Guocai Wang, Fangyuan Shao, Wenbo Chen, Chao Xia, Sheng Wang, Yaolan Li, Guangxiong Zhou, Zhong Liu (Source: Frontiers in Pharmacology)



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)



Generation of the Fip1l1–Pdgfra fusion gene using CRISPR/Cas genome editing

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

Generation of the Fip1l1–Pdgfra fusion gene using CRISPR/Cas genome editing Leukemia advance online publication, March 29 2016. doi:10.1038/leu.2016.62 Authors: M Vanden Bempt, S Demeyer, N Mentens, E Geerdens, C E De Bock, I Wlodarska & J Cools (Source: Leukemia)



MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis

Mon, 28 Mar 2016 21:37:01 +0100

The TALE-class homeoprotein MEIS1 specifically collaborates with HOXA9 to drive myeloid leukemogenesis. Although MEIS1 alone has only a moderate effect on cell proliferation in vitro, it is essential for the development of HOXA9-induced leukemia in vivo. Here, using murine models of leukemogenesis, we have shown that MEIS1 promotes leukemic cell homing and engraftment in bone marrow and enhances cell-cell interactions and cytokine-mediated cell migration. We analyzed global DNA binding of MEIS1 in leukemic cells as well as gene expression alterations in MEIS1-deficent cells and identified synaptotagmin-like 1 (Sytl1, also known as Slp1) as the MEIS1 target gene that cooperates with Hoxa9 in leukemogenesis. Replacement of SYTL1 in MEIS1-deficent cells restored both cell migration and engraf...



Mp63-01 a proposal for a novel peri-operative mortality risk assessment tool in contemporary patients treated with radical cystectomy

Mon, 28 Mar 2016 19:24:08 +0100

The Charlson comorbidity index (CCI) is the most widely used index score in retrospective analyses. However, several comorbid conditions included in this index, such as sever liver disease, AIDS, leukemia/lymphoma, are never seen in patients candidate to radical cystectomy (RC). Some other comorbid conditions, such as diabetes, and chronic pulmonary disease, are very frequently seen. Conversely, other conditions that are not accounted within that CCI index may represent better predictors of perioperative mortality. (Source: The Journal of Urology)

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Mp85-01 myocyte enhancer factor 2a (mef2a) is up-regulated in clear cell renal cell carcinoma

Mon, 28 Mar 2016 19:24:02 +0100

Mef2A is a master transcription factor involved in cellular metabolism, epithelial-mesenchymal transition and invasion. Normally expressed at high levels in heart and skeletal muscle, it has recently been identified in leukemia, breast and hepatocellular carcinomas. As a tumor with significant metabolic derangement, we hypothesized that Mef2A is up-regulated in ccRCC, where it promotes tumor growth, migration and invasion. (Source: The Journal of Urology)



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,...



The U.S. Throws Out $3 Billion In Cancer Drugs Every Year

Mon, 28 Mar 2016 15:39:32 +0100

(Reuters Health) - U.S. doctors and hospitals throw out almost $3 billion (roughly 2.7 billion euros) in unused cancer drugs each year because the medicines come in supersized single-use packages and excess medicine must be discarded for safety reasons, a recent paper suggests. Researchers focused on 20 expensive medicines that are given by injection or intravenous drip and require doses adjusted based on the patient’s body size. Often, the packages contain much more medicine than patients need, and the leftovers wind up in the trash. Even when much of the medicine goes in the garbage, patients pay for the whole vial, said lead author Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York City. “...



New hope for a type 2 diabetes cure

Mon, 28 Mar 2016 15:06:01 +0100

Gleevec, which is used in leukemia medications, holds promise for a dramatically more effective treatment of type 2 diabetes, report scientists. (Source: ScienceDaily Headlines)



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)

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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)



Glenmark Pharmaceuticals gets two ANDA approvals from USFDA

Mon, 28 Mar 2016 07:20:14 +0100

Glenmark Pharmaceuticals has received final approval from the US health regulator USFDA for oral contraceptives and leukemia treatment injection. (Source: The Economic Times Healthcare and Biotech News)



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...



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)

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DNA Repair in Despair‐Vitamin D Is not Fair

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

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



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)

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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...



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)



Cardiac tamponade as a symptom of the blast crisis of chronic myeloid leukemia

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

Publication date: Available online 28 March 2016 Source:The Kaohsiung Journal of Medical Sciences Author(s): Chiung-Tang Huang, Shih-Hao Yu, Yi-Hsien Chen, Sheng-Fung Lin (Source: The Kaohsiung Journal of Medical Sciences)



VIDEO: Cancer survivor meets her life-saver

Sun, 27 Mar 2016 15:44:25 +0100

A woman from Twickenham who survived leukaemia meets the man who donated the stem cells which saved her life. (Source: BBC News | Health | UK Edition)



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...

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Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.

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

Authors: Shen JX, Liu J, Li GW, Huang YT, Wu HT Abstract Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzy...



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,...



Prevalence of Leishmania infantum and co-infections in stray cats in northern Italy.

Sun, 27 Mar 2016 05:20:02 +0100

Authors: Spada E, Canzi I, Baggiani L, Perego R, Vitale F, Migliazzo A, Proverbio D Abstract Stray cats in the city of Milan, Italy, were tested for Leishmania infantum and other selected infections. Twenty-seven cats (30.0%) were seroreactive by indirect fluorescent antibody test (IFAT), with an antibody titer of 1:40 for 16 (17.7%) cats and 1:80 (cut-off for feline L. infantum infection) for 11 (12.2%) cats. One blood (1.1%) and one popliteal lymph node (1.1%) sample tested positive by real-time polymerase chain reaction; no oculoconjunctival swabs tested positive. Feline immunodeficiency virus, feline leukemia virus, and feline coronavirus (FCoV) seroprevalence determined by enzyme-linked immunosorbent assay was 6.1, 6.1, and 39.0%, respectively. Toxoplasma gondii, Bartonella he...



New hope for a type 2 diabetes cure

Sun, 27 Mar 2016 04:00:00 +0100

(Ulsan National Institute of Science and Technology(UNIST)) A research team, led by Professor Jang Hyun Choi (School of Life Sciences) of UNIST discovered Gleevec, which is used in leukemia medications, holds promise for a dramatically more effective treatment of type 2 diabetes. (Source: EurekAlert! - Cancer)



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...

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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...



Editorial Board

Sat, 26 Mar 2016 06:23:19 +0100

(Source: Clinical Lymphoma, Myeloma and Leukemia)



Table of Contents

Sat, 26 Mar 2016 06:23:19 +0100

(Source: Clinical Lymphoma, Myeloma and Leukemia)



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)

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Ibrutinib for Lymphocytic Leukemia Prompts Skin and Nail ChangesIbrutinib for Lymphocytic Leukemia Prompts Skin and Nail Changes

Fri, 25 Mar 2016 18:56:24 +0100

Although generally well tolerated, ibrutinib, a Bruton tyrosine kinase inhibitor effective against chronic lymphocytic leukemia (CLL), may lead to nail and hair abnormalities, according to a new report. Reuters Health Information (Source: Medscape Medical News Headlines)



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 ...



TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages.

Fri, 25 Mar 2016 16:53:02 +0100

Authors: Philip M, Chiu EY, Hajjar AM, Abkowitz JL Abstract Pathogenic bacteria have evolved multiple mechanisms to capture iron or iron-containing heme from host tissues or blood. In response, organisms have developed defense mechanisms to keep iron from pathogens. Very little of the body's iron store is available as free heme; rather nearly all body iron is complexed with heme or other proteins. The feline leukemia virus, subgroup C (FeLV-C) receptor, FLVCR, exports heme from cells. It was unknown whether FLVCR regulates heme-iron availability after infection, but given that other heme regulatory proteins are upregulated in macrophages in response to bacterial infection, we hypothesized that macrophages dynamically regulate FLVCR. We stimulated murine primary macrophages or macro...



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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Function of Membrane-Associated Proteoglycans in the Regulation of Satellite Cell Growth.

Fri, 25 Mar 2016 11:05:03 +0100

Authors: Song Y Abstract Muscle growth can be divided into embryonic and postnatal periods. During the embryonic period, mesenchymal stem cells proliferate and differentiate to form muscle fibers. Postnatal muscle growth (hypertrophy) is characterized by the enlargement of existing muscle fiber size. Satellite cells (also known as adult myoblasts) are responsible for hypertrophy. The activity of satellite cells can be regulated by their extracellular matrix (ECM). The ECM is composed of collagens, proteoglycans, non-collagenous glycoproteins, cytokines and growth factors. Proteoglycans contain a central core protein with covalently attached glycosaminoglycans (GAGs: chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate) and N- or O-linked glycosylation chains....



The Role of Leukemia Inhibitory Factor Receptor Signaling in Skeletal Muscle Growth, Injury and Disease.

Fri, 25 Mar 2016 11:05:03 +0100

This article will discuss the shared and distinct processes that LIFR cytokines regulate in a variety of experimental models with the common theme of skeletal muscle physiology. PMID: 27003396 [PubMed - in process] (Source: Advances in Experimental Medicine and Biology)



[In Brief] News at a glance

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

In science news around the world, SeaWorld announces that it will no longer breed orcas, China releases its first set of guidelines for the treatment of laboratory animals, a German mortician contracts Lassa fever in the first clear case of the disease's transmission outside of Africa, philanthropist Paul G. Allen launches a new bioscience research initiative, the U.S. National Science Foundation announces that it has indefinitely suspended a program to support museum biological collections, and more. Also corporate executive and leukemia survivor Greg Simon has been tapped to head Vice President Joe Biden's $1 billion "moonshot" to cure cancer. And Egypt's antiquities minister confirms that high-resolution radar scans of the walls of King Tutankhamun's tomb, taken last fall, have identifi...



[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...



TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy

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

TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy Leukemia advance online publication, March 25 2016. doi:10.1038/leu.2016.34 Authors: E Nievergall, J Reynolds, C H Kok, D B Watkins, M Biondo, S J Busfield, G Vairo, K Fuller, W N Erber, T Sadras, R Grose, D T Yeung, A F Lopez, D K Hiwase, T P Hughes & D L White (Source: Leukemia)

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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)



Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis

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

Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis Leukemia advance online publication, March 25 2016. doi:10.1038/leu.2016.53 Authors: Y Gu, W Zheng, J Zhang, X Gan, X Ma, Z Meng, T Chen, X Lu, Z Wu, W Huang & R Xu (Source: Leukemia)



Analysis of racial variations in disease characteristics, treatment patterns, and outcomes of patients with chronic lymphocytic leukemia

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

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



Molecules, Vol. 21, Pages 404: The Chemical Composition of Achillea wilhelmsii C. Koch and Its Desirable Effects on Hyperglycemia, Inflammatory Mediators and Hypercholesterolemia as Risk Factors for Cardiometabolic Disease

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

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fas...

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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)



Molecular Cytogenetic Analysis of Chromosome 8 Aberrations in Patients With Multiple Myeloma Examined in 2 Different Stages, at Diagnosis and at Progression/Relapse

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

Conclusion In the current study, chromosome 8 aberrations were highly heterogeneous, were presented at diagnosis in patients with advanced clinical stage, and were associated with worse overall survival. We have not confirmed the increase of frequency aberration of chromosome 8 in disease progression. The findings demonstrate the importance of fluorescence in situ hybridization examination of chromosome 8 in newly diagnosed patients with MM. Micro-Abstract This retrospective study of 62 patients with multiple myeloma examined at 2 different phases (diagnosis and progression/relapse), revealed chromosome 8 aberrations in 24 (38.7%) patients at diagnosis and in 29 (46.8%) patients at progression/relapse. We did not confirm a significant increase of chromosome 8 aberrations at progression/re...



Induction of apoptosis in human leukemia cells through an intrinsic pathway by cathachunine, a unique alkaloid isolated from Catharanthus roseus

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

Conclusion: An unprecedented bisindole alkaloid cathachunine which lost C-18′ and C-19′ was isolated from C. roseus. It exerted a potent antitumor effect toward human leukemia cells through the induction of apoptosis via an intrinsic pathway. Thus, this study provides evidence for a new lead compound from a natural source for anti-cancer investigations. Graphical abstract (Source: Phytomedicine)



Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma

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

Authors: L Ratner, D Rauch, H Abel, B Caruso, A Noy, S K Barta, S Parekh, J C Ramos, R Ambinder, A Phillips, J Harding, H H Baydoun, X Cheng & S Jacobson (Source: Blood Cancer Journal)



Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers.

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

Authors: Chang ET, Delzell E Abstract This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0-1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0-1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7-1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6-1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding ...

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Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer.

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

Authors: Haque A, Alam Q, Alam MZ, Azhar EI, Sait KH, Anfina N, Mushtaq G, Kamal MA, Rasool M Abstract Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts a...



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)



Leukocytoclastic vasculitis associated with hairy cell leukemia at diagnosis: a case report and review of the literature.

Thu, 24 Mar 2016 12:07:02 +0100

CONCLUSIONS: The clinical picture we have observed is of interest for the following reasons: i) it confirms an existing pathogenetic relationship between this lymphoproliferative disorder and its cutaneous manifestations, as suggested by the prompt resolution of the purpuric lesions upon cladribine administration; ii) it indicates that cladribine is an effective treatment for HCL-related paraneoplastic syndromes, including leukocytoclastic vasculitis; iii) the evolution and the outcomes of the paraneoplastic manifestations may be independent of those of the underlying leukemia, which showed less than a partial response to its initial treatment. PMID: 27002952 [PubMed - as supplied by publisher] (Source: Tumori)



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...

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Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia

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

The mechanism of action of imatinib is known to involve the Fas-mediated apoptosis pathway. Consequently inter-individual variations in this apoptosis pathway might be associated with imatinib response or resi... (Source: Journal of Translational Medicine)



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)



Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy

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

A novel functional‐genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in “big data” providing comprehensive information about the drugs’ targets and their functional genomics is proposed. In “process pharmacology”, drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high‐dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a shor...

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The presence of heparins during decidualization modulates the response of human endometrial stromal cells to IL-1β in vitro

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

Conclusions Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1β-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation. (Source: Journal of Assisted Reproduction and Genetics)



Glycosylation Status of CD43 Protein Is Associated with Resistance of Leukemia Cells to CTL-Mediated Cytolysis

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

In this study, we sought to identify cell-surface molecules associated with resistance of leukemia cells to cytotoxic T cell (CTL)-mediated cytolysis. To this end, we first established thousands of monoclonal antibodies (mAbs) that react with MLL/AF9 mouse leukemia cells. Only two of these mAbs, designated R54 and B2, bound preferentially to leukemia cells resistant to cytolysis by a tumor cell antigen–specific CTLs. The antigens recognized by these mAbs were identified by expression cloning as the same protein, CD43, although their binding patterns to subsets of hematopoietic cells differed significantly from each other and from a pre-existing pan-CD43 mAb, S11. The epitopes of R54 and B2, but not S11, were sialidase-sensitive and expressed at various levels on leukemia cells, suggestin...



Viruses, Vol. 8, Pages 88: Determinants of the Bovine Leukemia Virus Envelope Glycoproteins Involved in Infectivity, Replication and Pathogenesis

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

Interaction of viral envelope proteins with host cell membranes has been extensively investigated in a number of systems. However, the biological relevance of these interactions in vivo has been hampered by the absence of adequate animal models. Reverse genetics using the bovine leukemia virus (BLV) genome highlighted important functional domains of the envelope protein involved in the viral life cycle. For example, immunoreceptor tyrosine-based activation motifs (ITAM) of the envelope transmembrane protein (TM) are essential determinants of infection. Although cell fusion directed by the aminoterminal end of TM is postulated to be essential, some proviruses expressing fusion-deficient envelope proteins unexpectedly replicate at wild-type levels. Surprisingly also, a conserved N-linked gly...



Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

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

In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs), but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL). Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT) signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8). We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may ...



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)

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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 ...



Clinical impact of MYD88 mutations in chronic lymphocytic leukemia

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

(Source: Blood)



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. ...

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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)



Autoimmune cytopenias in patients with chronic lymphocytic leukemia treated with ibrutinib.

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

Authors: Vitale C, Ahn IE, Sivina M, Ferrajoli A, Wierda WG, Estrov Z, Konoplev SN, Jain N, O' Brien S, Farooqui M, Keating MJ, Wiestner A, Burger JA PMID: 27013651 [PubMed - as supplied by publisher] (Source: Haematologica)



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)

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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...



Alvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia.

Wed, 23 Mar 2016 16:51:02 +0100

Authors: Wiernik PH Abstract INTRODUCTION: Alvocidib, which has orphan drug designation in chronic lymphocytic leukemia (CLL) from the FDA and the EMA, is a plant-derived semisynthetic flavone that acts as a cyclin-dependent kinase inhibitor. It induces apoptosis in CLL cells in vitro and was introduced into clinical trials in CLL as an intravenous infusion in 1997, which proved disappointing. Since the drug avidly binds to plasma proteins, higher serum concentrations were required for clinical antileukemia activity than those suggested by in vitro studies. Subsequent studies utilizing bolus plus infusional doses revealed significant activity against CLL, even in patients with unfavorable characteristics. However, significant toxicity including high rates of major tumor lysis syndr...



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)



ClinicalThought: Cancer Immunotherapy

Wed, 23 Mar 2016 12:00:00 +0100

Learning Module - In this CME-certified educational module, CCO’s expert faculty examine the latest immunotherapeutic options, with associated adverse events, as well as their seamless integration into the clinical management of patients with various malignancies. (Source: Clinical Care Options Leukemia)



Ivy Rainbow's leukaemia battle is shared on Instagram

Wed, 23 Mar 2016 08:57:31 +0100

Nicole Jamieson's daughter Ivy, three, was diagnosed with leukaemia in October. Since, the family, from New South Wales, have been sharing updates on her journey on Instagram. (Source: the Mail online | Health)

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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)



Simplifying procedure for prediction of resistance risk in CML patients — Test of sensitivity to TKI ex vivo

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

Publication date: May 2016 Source:Blood Cells, Molecules, and Diseases, Volume 58 Author(s): Markéta Žáčková, Tereza Macháčková-Lopotová, Zuzana Ondráčková, Kateřina Kuželová, Hana Klamová, Jana Moravcová Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have dramatically improved chronic myeloid leukemia therapy. While imatinib remains to be the first line therapy, about 30% of patients develop resistance or intolerance to this drug and are recommended to switch to other TKIs. Nilotinib and dasatinib are currently implemented into the first line therapy and other inhibitors have already entered the clinical practice. This opens further questions on how to select the best TKI for each patient not only during the therapy but also at diagnosis. The individualized t...



Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

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

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the ...



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)

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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...



Peripheral arterial occlusive disease during ponatinib therapy after failure of imatinib: a case report

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

Summary What is known and objectivePeripheral vascular adverse events have been reported with ponatinib treatment in chronic myeloid leukaemia (CML) after failure of dasatinib or nilotinib. We here report peripheral arterial occlusive disease (PAOD) in a patient who had previously received only imatinib as tyrosine kinase inhibitor. Case descriptionThe patient was a 70‐year‐old man with no history of cardiovascular disease. He developed arterial hypertension 5 months after the initiation of ponatinib and PAOD 41 months later. What is new and conclusionPeripheral arterial occlusive disease can occur several years after the initiation of ponatinib in patients who had previously received only imatinib. Long‐term surveillance is required for preventing the complications of ponatinib‐as...



Transient Potential Receptor Melastatin-2 (TRPM2) Does Not Influence Murine MLL-AF9 Driven AML Leukemogenesis or in Vitro Response to Chemotherapy

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

Transient potential receptor melastatin-2 (TRPM2) is a non-selective cationic, Ca2+ permeable transmembrane pore that is preferentially expressed in cells of the myeloid lineage, and modulates signaling pathways converging onto NF-kB. This is of potential interest for AML therapy, as NF-κB signaling is emerging as a key pathway mediating drug resistance and leukemia initiating cell survival in AML, and inhibition of NF-κB signaling has been shown to be synergistic with chemotherapy. TRPM2 is overexpressed in AML compared to normal bone marrow, with highest levels in the FAB M3-6 subtypes. (Source: Experimental Hematology)



Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist.

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

Authors: Maus MV, Levine BL Abstract : The field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)-modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T-cell signaling and costimulatory domains that can be used to reprogram a patient's T cells to specifically target tumor cells. CAR T-cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T-cell therapy-associated toxicities, including cytokine rele...