Subscribe: PubMed: Haematologica[jour]
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=0Ea95KmC8Hbpg01c4bSv_KK0gPk6EdN_Xzs3elsDf6N
Added By: Feedage Forager Feedage Grade B rated
Language: English
Tags:
acute myeloid  cells  fms tyrosine  kinase  leukemia  myeloid leukemia  senescence  spi  survival  tyrosine kinase  tyrosine 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: PubMed: Haematologica[jour]

pubmed: Haematologica[jour]



NCBI: db=pubmed; Term=Haematologica[jour]



 



Rac1 functions downstream of miR-142 in regulation of erythropoiesis.
Related Articles

Rac1 functions downstream of miR-142 in regulation of erythropoiesis.

Haematologica. 2017 Sep 14;:

Authors: Rivkin N, Chapnik E, Birger Y, Yanowski E, Curato C, Mildner A, Porat Z, Amir G, Izraeli S, Jung S, Hornstein E

Abstract
"-".

PMID: 28912177 [PubMed - as supplied by publisher]




Anexelekto /MER Tyrosine Kinase inhibitor ONO-7475 growth arrests and kills FMS-Like Tyrosine Kinase 3-Internal Tandem Duplication Mutant Acute Myeloid Leukemia cells by diverse mechanisms.
Related Articles

Anexelekto /MER Tyrosine Kinase inhibitor ONO-7475 growth arrests and kills FMS-Like Tyrosine Kinase 3-Internal Tandem Duplication Mutant Acute Myeloid Leukemia cells by diverse mechanisms.

Haematologica. 2017 Sep 14;:

Authors: Ruvolo PP, Ma H, Ruvolo VR, Zhang X, Mu H, Schober W, Hernandez I, Gallardo M, Khoury J, Cortes J, Andreeff M, Post SM

Abstract
Nearly one-third of patients with acute myeloid leukemia have FMS-Like Tyrosine Kinase 3 mutations and thus have poor survival prospects. Receptor tyrosine kinase Anexelekto is critical for FMS-Like Tyrosine Kinase 3 signaling and participates in FMS-Like Tyrosine Kinase 3 inhibitor resistance mechanisms. Thus, strategies targeting Anexelekto could prove useful for acute myeloid leukemia therapy. ONO-7475 is an inhibitor with high specificity for Anexelekto and MER Tyrosine Kinase. Here we report that ONO-7475 potently arrested growth and induced apoptosis in acute myeloid leukemia with internal tandem duplication mutation of FMS-Like Tyrosine Kinase 3. MER Tyrosine Kinase-lacking MOLM13 cells were sensitive to ONO-7475 while MER Tyrosine Kinase -expressing OCI-AML3 cells were resistant, suggesting that the drug acts via Anexelekto in acute myeloid leukemia cells. Reverse phase protein analysis of ONO-7475 treated cells revealed that cell cycle regulators like Cyclin Dependent Kinase 1, Cyclin B1, Polo-like Kinase 1, and Retinoblastoma were suppressed. ONO-7475 suppressed Cyclin Dependent Kinase 1, Cyclin B1, Polo-like Kinase 1gene expression suggesting that Anexelekto may regulate the cell cycle at least in part via transcriptional mechanisms. Importantly, ONO-7475 was effective in a human FMS-Like Tyrosine Kinase 3 with Internal Tandem Duplication mutant murine xenograft model. Mice fed a diet containing ONO-7475 exhibited significantly longer survival and, interestingly, blocked leukemia cell infiltration in the liver. In summary, ONO-7475 effectively kills acute myeloid leukemia cells in vitro and in vivo by mechanisms that involve disruption of diverse survival and proliferation pathways.

PMID: 28912176 [PubMed - as supplied by publisher]




In vitro evidence of complement activation in patients with sickle cell disease.
Related Articles

In vitro evidence of complement activation in patients with sickle cell disease.

Haematologica. 2017 Sep 14;:

Authors: Gavriilaki E, Mainou M, Christodoulou I, Koravou EE, Paleta A, Touloumenidou T, Papalexandri A, Athanasiadou A, Apostolou C, Klonizakis P, Anagnostopoulos A, Vlachaki E

PMID: 28912175 [PubMed - as supplied by publisher]




Senescence is a Spi1/PU.1-induced anti-proliferative mechanism in primary hematopoietic cells.
Related Articles

Senescence is a Spi1/PU.1-induced anti-proliferative mechanism in primary hematopoietic cells.

Haematologica. 2017 Sep 14;:

Authors: Delestré L, Hengxiang C, Esposito M, Quiveron C, Mylonas E, Penard-Lacronique V, Bischof O, Guillouf C

Abstract
Transcriptional deregulation caused by epigenetic or genetic alterations is a major cause of leukemic transformation. The Spi1/PU.1 transcription factor is a key regulator of many steps of hematopoiesis, and limits self-renewal of hematopoietic stem cells. The deregulation of its expression or activity contributes to leukemia, in which Spi1 can be either an oncogene or a tumor suppressor. Here, we explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cells expansion, and thus prevents the development of leukemia. We show that Spi1 overexpression triggers cellular senescence both in primary fibroblasts and hematopoietic cells. Erythroid and myeloid lineages are both prone to Spi1-induced senescence. In hematopoietic cells, Spi1-induced senescence requires its DNA-binding activity and a functional p38MAPK14 pathway but is independent of a DNA-damage response. In contrast, in fibroblasts, Spi1-induced senescence is triggered by a DNA-damage response. Importantly, using our well-established Spi1 transgenic leukemia mouse model, we demonstrate that Spi1 overexpression also induces senescence in erythroid progenitors of the bone marrow in vivo before the onset of the pre-leukemic phase of the erythroleukemia. Remarkably, the senescence response is lost during the progression of the disease and erythroid blasts do not display a higher expression of Dec1 and CDKN1A, two of the induced-senescence markers in young animals. These results bring indirect evidence that leukemia develops from cells having bypassed Spi1-induced senescence. Overall, our results reveal senescence as a Spi1-induced anti-proliferative mechanism that may be a safeguard against the development of acute myeloid leukemia.

PMID: 28912174 [PubMed - as supplied by publisher]




Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials.
Related Articles

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials.

Haematologica. 2017 Sep 14;:

Authors: Eichenauer DA, Becker I, Monsef I, Chadwick N, de Sanctis V, Federico M, Fortpied C, Gianni AM, Henry-Amar M, Hoskin P, Johnson P, Luminari S, Bellei M, Pulsoni A, Sydes MR, Valagussa P, Viviani S, Engert A, Franklin J

Abstract
Treatment intensification to maximize disease control and reduced-intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the present meta-analysis based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs chemotherapy alone; more extended vs involved-field radiotherapy; radiation at higher doses vs radiation at 20 Gy; more vs fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival (p=0.007) rates as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (p=0.0028). No progression-free or overall survival differences were observed between combined-modality and chemotherapy alone, but more secondary malignancies were seen after combined-modality (p=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment of Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

PMID: 28912173 [PubMed - as supplied by publisher]