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Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia.
In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low. Importantly, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 have an unfavorable disease course with short overall survival and time to second treatment. COBLL1 serves as an independent molecular marker for overall surviv...
Source: Haematologica - November 9, 2017 Category: Hematology Authors: Plešingerová H, Janovská P, Mishra A, Smyčková L, Poppová L, Libra A, Plevová K, Ovesná P, Radová L, Doubek M, Pavlová Š, Pospíšilová Š, Bryja V Tags: Haematologica Source Type: research

Maternal embryonic leucine zipper kinase is a novel target for proliferation associated high-risk myeloma.
Abstract Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitr...
Source: Haematologica - November 9, 2017 Category: Hematology Authors: Bolomsky A, Heusschen R, Schlangen K, Stangelberger K, Muller J, Schreiner W, Zojer N, Caers J, Ludwig H Tags: Haematologica Source Type: research

Labile plasma iron levels predict survival in patients with lower-risk Myelodysplastic syndromes.
CONCLUSION: toxic iron species occurred in all transfusion dependent patients and in transfusion independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion dependent patients. This trial was registered at www.clinicaltrials.gov as #NCT00600860. PMID: 29122992 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - November 9, 2017 Category: Hematology Authors: de Swart L, Reiniers C, Bagguley T, van Marrewijk C, Bowen D, Hellström-Lindberg E, Tatic A, Symeonidis A, Huls G, Cermak J, van de Loosdrecht AA, Garelius H, Culligan D, Macheta M, Spanoudakis M, Panagiotidis P, Krejci M, Blijlevens N, Langemeijer S, Dr Tags: Haematologica Source Type: research

The microenvironmental stromal cells abrogate NF- κB inhibitor induced apoptosis in chronic lymphocytic leukemia.
The microenvironmental stromal cells abrogate NF-κB inhibitor induced apoptosis in chronic lymphocytic leukemia. Haematologica. 2017 Nov 09;: Authors: Simon-Gabriel CP, Foerster K, Saleem S, Bleckmann D, Benkisser-Petersen M, Thornton N, Umezawa K, Decker S, Burger M, Veelken H, Claus R, Dierks C, Duyster J, Zirlik K Abstract NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be cruc...
Source: Haematologica - November 9, 2017 Category: Hematology Authors: Simon-Gabriel CP, Foerster K, Saleem S, Bleckmann D, Benkisser-Petersen M, Thornton N, Umezawa K, Decker S, Burger M, Veelken H, Claus R, Dierks C, Duyster J, Zirlik K Tags: Haematologica Source Type: research

Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia after allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of European Society of Blood and Marrow Transplantation.
M, Arnold R, De Witte T, Robin M, Kröger N Abstract No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcome and risk factors in 698 patients, treated with different strategies. Median overall survival from relapse was 4.7 months (4.1-5.3), 2-year survival was 17.7% (14.8-21.2%). Shorter remission after transplantation (p
Source: Haematologica - November 3, 2017 Category: Hematology Authors: Schmid C, de Wreede LC, van Biezen A, Finke J, Ehninger G, Ganser A, Volin L, Niederwieser D, Beelen D, Alessandrino P, Kanz L, Schleuning M, Passweg J, Veelken H, Maertens J, Cornelissen JJ, Blaise D, Gramatzki M, Milpied N, Yakub-Agha I, Mufti G, Rovira Tags: Haematologica Source Type: research

Knockdown of TP53 in ASXL1 negative background rescues apoptotic phenotype of human hematopoietic stem and progenitor cells but without overt malignant transformation.
PMID: 29101206 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - November 3, 2017 Category: Hematology Authors: Hilgendorf S, Vellenga E Tags: Haematologica Source Type: research

The ferroportin disease: pathogenesis, diagnosis and treatment.
Abstract The Ferroportin Disease is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of commonest cause of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In the ferroportin disease, loss-of-function mutations of FPN1 limit but do not impair iron-export in enterocytes, but severely affects iron-transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum tra...
Source: Haematologica - November 3, 2017 Category: Hematology Authors: Pietrangelo A Tags: Haematologica Source Type: research

EBV-associated primary nodal T/NK-cell lymphoma shows distinct molecular signature and copy number changes.
In this study, we assessed the relationship between nodal and extranodal EBV-positive T/NK-cell lymphomas using gene expression profiling and copy number aberration analyses. We performed GEP and CNA analysis on 66 cases of EBV-associated T/NK-cell lymphoma from nodal and extranodal sites, and correlated the molecular signatures with clinicopathologic features. Three distinct molecular clusters were identified with one enriched for nodal presentation and loss of 14q11.2 (TCRA loci). TNKL with nodal presentation (N-group) was significantly associated with older age, lack of nasal involvement, and T-cell lineage compared to ...
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Ng SB, Chung TH, Kato S, Nakamura S, Takahashi E, Ko YH, Khoury JD, Yin CC, Soong R, Jeyasekharan AD, Hoppe MM, Selvarajan V, Tan SY, Lim ST, Ong CK, Nairismägi ML, Maheshwari P, Choo SN, Fan S, Lee CK, Chuang SS, Chng WJ Tags: Haematologica Source Type: research

Response to MEK inhibition with trametinib and tyrosine kinase inhibition with imatinib in multifocal histiocytic sarcoma.
PMID: 29097496 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Voruz S, Cairoli A, Naveiras O, de Leval L, Missiaglia E, Homicsko K, Michielin O, Blum S Tags: Haematologica Source Type: research

MDS1 and EVI1 complex locus (MECOM): a novel candidate gene for hereditary hematological malignancies.
PMID: 29097497 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Ripperger T, Hofmann W, Koch JC, Shirneshan K, Haase D, Wulf G, Issing PR, Karnebogen M, Schmidt G, Auber B, Schlegelberger B, Illig T, Zirn B, Steinemann D Tags: Haematologica Source Type: research

Short-term administration of JAK2 inhibitors reduces splenomegaly in mouse models of ß-thalassemia intermedia and major.
Short-term administration of JAK2 inhibitors reduces splenomegaly in mouse models of ß-thalassemia intermedia and major. Haematologica. 2017 Nov 02;: Authors: Casu C, Lo Presti V, Oikonomidou PR, Melchiori L, Abdulmalik O, Ramos P, Rivella S PMID: 29097498 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Casu C, Lo Presti V, Oikonomidou PR, Melchiori L, Abdulmalik O, Ramos P, Rivella S Tags: Haematologica Source Type: research

Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide or azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia.
Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide or azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia. Haematologica. 2017 Nov 02;: Authors: Medeiros BC, McCaul K, Kambhampati S, Pollyea DA, Kumar R, Silverman LR, Kew A, Saini L, Beach CL, Vij R, Wang X, Zhong J, Gale RP Abstract Therapy of acute myeloid leukemia in older persons is associated with poor outcomes because of intolerance to intensive therapy, resistant disease and co-morbidities. This multi-center, randomized, open-label, phase-2 trial compared safety and efficac...
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Medeiros BC, McCaul K, Kambhampati S, Pollyea DA, Kumar R, Silverman LR, Kew A, Saini L, Beach CL, Vij R, Wang X, Zhong J, Gale RP Tags: Haematologica Source Type: research

A bio-clinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma.
The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2. In addition, 97 formalin-fixed, paraffin-embedded tissue sam...
Source: Haematologica - November 2, 2017 Category: Hematology Authors: Bosch M, Akhter A, Chen BE, Mansoor A, Lebrun D, Good D, Crump M, Shepherd L, Scott DW, Stewart DA, Canadian Cancer Trials Group Tags: Haematologica Source Type: research

Understanding the extracellular matrix in acute myeloid leukemia.
PMID: 29079646 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 29, 2017 Category: Hematology Authors: Izzi V, Heljasvaara R, Pihlajaniemi T Tags: Haematologica Source Type: research

Late effects of blood and marrow transplantation.
PMID: 29079647 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 29, 2017 Category: Hematology Authors: Banerjee R, Luskin MR, Loren AW Tags: Haematologica Source Type: research

Inhibition of focal adhesion kinase overcomes resistance of mantle cell lymphoma to ibrutinib in the bone marrow microenvironment.
Abstract Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells cocultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi based focal adhesion kinase silencing was performed. We could show that focal adhesion kinase is highly ex...
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Rudelius M, Rosenfeldt MT, Leich E, Rauert-Wunderlich H, Solimando AG, Beilhack A, Ott G, Rosenwald A Tags: Haematologica Source Type: research

Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage.
In conclusion, hypoxanthine is an in vitro metabolic marker of the RBC storage lesion that negatively correlates with post-transfusion recovery in vivo. Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates. PMID: 29079593 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Nemkov T, Sun K, Reisz JA, Song A, Yoshida T, Dunham A, Wither MJ, Francis RO, Roach RC, Dzieciatkowska M, Rogers SC, Doctor A, Kriebardis A, Antonelou M, Papassideri I, Young C, Thomas T, Hansen KC, Spitalnik SL, Xia Y, Zimring JC, Hod EA, D'Alessandro A Tags: Haematologica Source Type: research

Chromothripsis is linked to TP53 alteration, cell cycle impairment, and dismal outcome in acute myeloid leukemia with complex karyotype.
K, Bullinger L PMID: 29079594 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Rücker FG, Dolnik A, Blätte TJ, Teleanu V, Ernst A, Thol F, Heuser M, Ganser A, Döhner H, Döhner K, Bullinger L Tags: Haematologica Source Type: research

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassaemia major: the DEEP-3 multi-centre observational safety study.
PMID: 29079595 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Botzenhardt S, Felisi M, Bonifazi D, Del Vecchio GC, Putti MC, Kattamis A, Ceci A, Wong IC, Neubert A, DEEP Consortium Tags: Haematologica Source Type: research

Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway.
r U Abstract The effects of erythropoietin on osteoblasts and bone formation are controversially discussed. Since patients with myelodysplastic syndromes often display excessively high erythropoietin level, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblasts mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblasts mineralization ...
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Balaian E, Wobus M, Weidner H, Baschant U, Stiehler M, Ehninger G, Bornhäuser M, Hofbauer LC, Rauner M, Platzbecker U Tags: Haematologica Source Type: research

Single-molecule DNA sequencing of acute myeloid leukemia and myelodysplastic syndromes with multiple TP53 alterations.
re-Bertrand T, Soussi T PMID: 29079597 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Lodé L, Ameur A, Coste T, Ménard A, Richebourg S, Gaillard JB, Le Bris Y, Béné MC, Lavabre-Bertrand T, Soussi T Tags: Haematologica Source Type: research

GA101 P329G LALA, a variant of obinutuzumab with abolished ADCC, ADCP and CDC function but retained cell death induction, is as efficient as rituximab in B cell depletion and antitumor activity.
n C PMID: 29079598 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Herter S, Herting F, Muth G, van Puijenbroek E, Schlothauer T, Ferrara C, Brady K, Lang S, Bacac M, Mössner E, Umana P, Klein C Tags: Haematologica Source Type: research

Predictive value of MRD in Ph+ ALL treated with imatinib in the EsPhALL study, based on IG/TR and BCR/ABL1 methodologies.
Conter V, Schrappe M, Valsecchi MG, Biondi A Abstract The prognostic value of Minimal Residual Disease in Ph+ childhood acute lymphoblastic leukemia treated with tyrosine kinase inhibitors is not fully established. We detected MRD by RQ-PCR of rearranged immunoglobulin/T-cell receptor genes and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving BFM high risk therapy and post induction intermittent imatinib (EsPhALL study). MRD was monitored after induction (TP1), consolidation Phase IB (TP2), HR Blocks, reinductions, end of therapy. MRD negativity increased progressively over t...
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Cazzaniga G, De Lorenzo P, Alten J, Röttgers S, Hancock J, Saha V, Castor A, Madsen HO, Gandemer V, Cavé H, Leoni V, Köhler R, Ferrari GM, Bleckmann K, Pieters R, Van der Velden V, Stary J, Zuna J, Escheric G, Zur Stadt U, Aricò M, Conter V, Schrappe Tags: Haematologica Source Type: research

Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the EXELS study.
Abstract Evaluation of Xagrid® Efficacy and Long-term Safety, a Phase IV, prospective, non interventional study performed in 13 European countries enrolled high risk essential thrombocythemia patients treated with cytoreductive therapy. Primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid®) (n=804), other cytoreductive therapy (n=2666), anagrelide + other cytoreductive therapy (n=141). Median age was 56 vs 70 years for anagrelide vs other cytoreductive therapy. Event rates (patients ...
Source: Haematologica - October 27, 2017 Category: Hematology Authors: Birgegard G, Besses C, Griesshammer M, Gugliotta L, Harrison CN, Hamdani M, Wu J, Achenbach H, Kiladjian JJ Tags: Haematologica Source Type: research

Expansion of EPOR-negative macrophages besides erythroblasts by elevated EPOR signaling in erythrocytosis mouse models.
Abstract Activated EPO receptor (EPOR) signaling causes erythrocytosis. The important role of macrophages for the erythroid expansion and differentiation process has been reported, both in baseline and stress erythropoiesis. However, the significance of EPOR signaling for regulation of macrophages contributing to erythropoiesis has not been fully understood. Here we show that EPOR signaling activation quickly expands both erythrocytes and macrophages in vivo in mouse models of primary and secondary erythrocytosis. To mimic the chimeric condition and expansion of the disease clone in the polycythemia vera patients,...
Source: Haematologica - October 19, 2017 Category: Hematology Authors: Wang J, Hayashi Y, Yokota A, Xu Z, Zhang Y, Huang R, Yan X, Liu H, Ma L, Azam M, Bridges JP, Cancelas JA, Kalfa TA, An X, Xiao Z, Huang G Tags: Haematologica Source Type: research

Panobinostat monotherapy and combination therapy in patients with acute myeloid leukemia, results from two clinical trials.
PMID: 29051280 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 19, 2017 Category: Hematology Authors: Schlenk R, Krauter J, Raffoux E, Kreuzer KA, Schaich M, Noens L, Pabst T, Vusirikala M, Bouscary D, Spencer A, Candoni A, Sierra Gil J, Berkowitz N, Weber HJ, Ottmann O Tags: Haematologica Source Type: research

Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after 15 years of follow-up.
Abstract The National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort enrolls patients with the four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome, and follows them with a common comprehensive protocol. The current analysis includes more than double the numbers of patients and person-years since our first report in 2010. Patients with Fanconi anemia and dyskeratosis congenita developed head and neck and anogenital squamous cell carcinomas at rates that are hundreds-fold greater than the general population. In competing risk analyses...
Source: Haematologica - October 19, 2017 Category: Hematology Authors: Alter BP, Giri N, Savage SA, Rosenberg PS Tags: Haematologica Source Type: research

Small bone marrow adipocytes predict poor prognosis in acute myeloid leukaemia.
PMID: 29051282 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 19, 2017 Category: Hematology Authors: Lu W, Weng W, Zhu Q, Zhai Y, Wan Y, Liu H, Yang S, Yu Y, Wei Y, Shi J Tags: Haematologica Source Type: research

Hsp90 inhibition disrupts JAK-STAT signaling and leads to reductions in splenomegaly in patients with MPNs.
PMID: 29051283 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 19, 2017 Category: Hematology Authors: Hobbs GS, Hanasoge Somasundara AV, Kleppe M, Litvin R, Arcila M, Ahn J, Mckenney AS, Knapp K, Ptashkin R, Weinstein H, Heinemann MH, Francis J, Chanel S, Berman E, Mauro M, Tallman MS, Heaney ML, Levine RL, Rampal RK Tags: Haematologica Source Type: research

Clinical severity in adult warm autoimmune hemolytic anemia and its relationship to antibody specificity.
vas M Abstract "-". PMID: 29025905 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Chadebech P, Loustau V, Janvier D, Languille L, Ripa J, Tamagne M, Bierling P, Djoudi R, Godeau B, Michel M, Pirenne F, Mahévas M Tags: Haematologica Source Type: research

Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells.
erg J Abstract The development of anti-factor VIII antibodies represents a major complication in the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4+ T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4+ T cells, we previously developed a mass-spectrometry based method to identify factor VIII derived peptides that are presented on human leucocyte antigen (...
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Peyron I, Hartholt RB, Pedró-Cos L, van Alphen F, Ten Brinke A, Lardy N, Meijer S, Voorberg J Tags: Haematologica Source Type: research

Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells vulnerability to DNA-damaging agents.
ea M Abstract Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia, and thus represents potential therapeutic target. Recent studies demonstrate that SIRT6, a NAD+-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity in different tumor cells. Here, we demonstrate that also CD34+ blasts from Acute Myeloid Leukemia patients show ongoing DNA damage and SIRT6 overexpression. Indeed, we identified a poor-prognostic subset of patients, with widespread instability, which relies on SIRT6 to compensate for DNA-replication stress. As resul...
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Cagnetta A, Soncini D, Orecchioni S, Talarico G, Minetto P, Guolo F, Retali V, Colombo N, Carminati E, Clavio M, Miglino M, Bergamaschi M, Nahimana A, Duchosal M, Todoerti K, Neri A, Passalacqua M, Bruzzone S, Nencioni A, Bertolini F, Gobbi M, Lemoli RM, Tags: Haematologica Source Type: research

A germ-line deletion of APOBEC3B does not contribute to subtype-specific childhood acute lymphoblastic leukemia etiology.
PMID: 29025908 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Wallace AD, Francis SS, Shao X, de Smith AJ, Walsh KM, Mckean-Cowdin R, Ma X, Dahl G, Barcellos LF, Wiemels JL, Metayer C Tags: Haematologica Source Type: research

Histone deacetylase inhibitors downregulate CCR4 expression and decrease mogamulizumab efficacy in CCR4-positive mature T-cell lymphomas.
In this study, we examined the in vitro synergistic effects of mogamulizumab and HDAC inhibitors against various T-cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4 in various T-cell lymphoma cell lines and found it was downregulated upon treatment with vorinostat, a pan-HDAC inhibitor. Next, we used isoform-specific HDAC inhibitors and siRNAs to determine the HDAC isoform involved in the regulation of CCR4, and demonstrated that romidepsin, a class I selective HDAC inhibitor, reduced CCR4 most efficiently. Moreover, among class I HDACs, the HDAC2 knockdown led to a reduction of CCR4 in lympho...
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Kitadate A, Ikeda S, Abe F, Takahashi N, Shimizu N, Matsue K, Tagawa H Tags: Haematologica Source Type: research

Protein arginine methyltransferase 6 controls erythroid gene expression and differentiation of human CD34+ progenitor cells.
Abstract Hematopoietic differentiation is driven by transcription factors, which orchestrate a fine tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type specific gene expression programs. These programs are stabilized by the epigenetic activity of recruited chromatin modifying cofactors. An example gives the association of the transcription factor RUNX1 with the protein arginine methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However, little is known about the specific influence of PRMT6 on this import...
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Herkt SC, Kuvardina ON, Herglotz J, Schneider L, Meyer A, Pommerenke C, Salinas-Riester G, Seifried E, Bonig H, Lausen J Tags: Haematologica Source Type: research

Treat or palliate: Outcomes of hyperelderly myeloma patients.
PMID: 29025911 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Panitsas F, Kothari J, Vallance G, Djebbari F, Ferguson L, Sultanova M, Ramasamy K Tags: Haematologica Source Type: research

Variable outcome and methylation status according to CEBPA mutant type in double-mutated acute myeloid leukemia patients and the possible implications for treatment.
Abstract Although CEBPA double-mutated (CEBPADM) acute myeloid leukemia is considered to be favorable-risk disease, relapse remains a major cause of treatment failure. Most CEBPADM patients have a classic biallelic mutant combination with an N-terminal mutation leading to production of p30 protein plus a C-terminal loss-of-function in-frame indel mutation (CEBPAClassic-DM), but approximately one-third of cases have one or more non-classic mutations, with diverse combinations reported, and there is little information on the consequences of such mutants. We evaluated outcome in a cohort of 104 CEBPADM patients, 79 C...
Source: Haematologica - October 12, 2017 Category: Hematology Authors: El-Sharkawi D, Sproul D, Allen CG, Feber A, Wright M, Hills RK, Linch DC, Gale RE Tags: Haematologica Source Type: research

Analyses of the FranceCoag cohort support immunogenicity differences among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A.
Abstract Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the inhibitor incidence in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated patient cohort was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII
Source: Haematologica - October 12, 2017 Category: Hematology Authors: Calvez T, Chambost H, d'Oiron R, Dalibard V, Demiguel V, Doncarli A, Gruel Y, Huguenin Y, Lutz P, Rothschild C, Vinciguerra C, Goudemand J, FranceCoag Collaborators Tags: Haematologica Source Type: research

Pattern of somatic mutations in patients with Waldenstr öm macroglobulinemia or IgM monoclonal gammopathy of undetermined significance.
Pattern of somatic mutations in patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance. Haematologica. 2017 Oct 05;: Authors: Varettoni M, Zibellini S, Defrancesco I, Ferretti VV, Rizzo E, Malcovati L, Gallì A, Della Porta MG, Boveri E, Arcaini L, Candido C, Paulli M, Cazzola M Abstract We analyzed MYD88 and CXCR4 mutation status of 260 patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance using allele-specific real time quantitative PCR and Sanger sequencing respectively. A subgroup of 119 ...
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Varettoni M, Zibellini S, Defrancesco I, Ferretti VV, Rizzo E, Malcovati L, Gallì A, Della Porta MG, Boveri E, Arcaini L, Candido C, Paulli M, Cazzola M Tags: Haematologica Source Type: research

Catalytically inactive Gla-domainless factor Xa binds to TFPI and restores ex vivo coagulation in hemophilia plasma.
PMID: 28983056 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Ersayin A, Thomas A, Seyve L, Thielens N, Castellan M, Marlu R, Polack B, Dagher MC Tags: Haematologica Source Type: research

Introducing high-throughput sequencing into mainstream of genetic diagnosis practice in inherited platelet disorders.
van der Reijden BA, Morgan NV, Watson SP, Vicente V, Hernández-Rivas JM, Rivera J, González-Porras JR, Project, Group of the Castilla y Leon Society of Thrombosis and Haemostasis Abstract Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in platelet production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventive treatments. Until recently, this has been performed by Sanger sequencing of a limited number of candidate genes. High-throughput sequencing is revolutionizing genetic diagnosis of diseases, including ...
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Bastida JM, Lozano ML, Benito R, Janusz K, Palma-Barqueros V, Del Rey M, Hernández-Sánchez JM, Riesco S, Bermejo N, González-García H, Rodriguez-Alén A, Aguilar C, Sevivas T, López-Fernández MF, Marneth AE, van der Reijden BA, Morgan NV, Watson SP, Tags: Haematologica Source Type: research

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome.
This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of myelodysplastic syndrome patients registered in the statewide South Australian-MDS registry. Median age of the 817 patients was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization. While alloimmunization was significantly higher in IPSS-R Very Low, Low and Intermediate risk groups compared to High and Very High groups (p=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell ...
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Singhal D, Kutyna MM, Chhetri R, Wee LYA, Hague S, Nath L, Nath SV, Sinha R, Wickham N, Lewis ID, Ross DM, Bardy PG, To LB, Reynolds J, Wood EM, Roxby DJ, Hiwase DK Tags: Haematologica Source Type: research

Pro-inflammatory proteins S100A9 and TNF α suppress erythropoietin elaboration in myelodysplastic syndromes.
Pro-inflammatory proteins S100A9 and TNFα suppress erythropoietin elaboration in myelodysplastic syndromes. Haematologica. 2017 Oct 05;: Authors: Cluzeau T, McGraw KL, Irvine B, Masala E, Ades L, Basiorka AA, Maciejewski JP, Auberger P, Wei S, Fenaux P, Santini V, List A Abstract Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating TNFα and IL-1β production. The role of MDS-related inflammatory proteins in endogenous Epo regulation...
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Cluzeau T, McGraw KL, Irvine B, Masala E, Ades L, Basiorka AA, Maciejewski JP, Auberger P, Wei S, Fenaux P, Santini V, List A Tags: Haematologica Source Type: research

Results and conclusions of the European Intergroup EURO-LB02 Trial in children and adolescents with lymphoblastic lymphoma.
Abstract In the European Intergroup EURO-LB02 Trial, children and adolescents with lymphoblastic lymphoma underwent the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster protocol without prophylactic cranial radiotherapy. Primary aims were to test whether replacing prednisone with dexamethasone during induction increases EFS in the T-cell lymphoblastic lymphoma subgroup and whether therapy duration can be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here, we report on the secondary aims of the study: whether the results ...
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Landmann E, Burkhardt B, Zimmermann M, Meyer U, Woessmann W, Klapper W, Wrobel G, Rosolen A, Pillon M, Escherich G, Attarbaschi A, Beishuizen A, Mellgren K, Wynn R, Ratei R, Plesa A, Schrappe M, Reiter A, Bergeron C, Patte C, Bertrand Y Tags: Haematologica Source Type: research

BCR-ABL1 compound mutants display differential and dose-dependent responses to ponatinib.
PMID: 28983061 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 5, 2017 Category: Hematology Authors: Byrgazov K, Lucini CB, Valent P, Hantschel O, Lion T Tags: Haematologica Source Type: research

Rapamycin targets several pathophysiological features of immune-mediated bone marrow failure in murine models.
PMID: 28965088 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2017 Category: Hematology Authors: Weston WW, Jurecic V, Jurecic R Tags: Haematologica Source Type: research

Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study.
Abstract Intravenous rituximab plus chemotherapy is standard treatment for diffuse large B-cell lymphoma. A subcutaneous formulation of rituximab is expected to simplify and shorten drug preparation and administration, and to reduce treatment burden. MabEase (NCT01649856) examined efficacy, safety and patient satisfaction with subcutaneous rituximab plus chemotherapy in treatment-naïve patients with diffuse large B-cell lymphoma. Patients were randomized 2:1 to subcutaneous rituximab (intravenous 375 mg/m(2) cycle 1; subcutaneous 1,400 mg cycles 2-8) or intravenous rituximab (375 mg/m(2) cycles 1-8) plus cycl...
Source: Haematologica - September 21, 2017 Category: Hematology Authors: Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M Tags: Haematologica Source Type: research

High prevalence of relapse in children with Philadelphia-like acute lymphoblastic leukemia despite risk-adapted treatment.
, Sutton R, White DL PMID: 28935844 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 21, 2017 Category: Hematology Authors: Heatley SL, Sadras T, Kok CH, Nievergall E, Quek K, Dang P, McClure B, Venn N, Moore S, Suttle J, Law T, Ng A, Muskovic W, Norris MD, Revesz T, Osborn M, Moore AS, Suppiah R, Fraser C, Alvaro F, Hughes TP, Mullighan CG, Marshall GM, Dalla Pozza L, Yeung D Tags: Haematologica Source Type: research

Rituximab biosimilar evaluated by network meta-analysis.
PMID: 28935845 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 21, 2017 Category: Hematology Authors: Chiumente M, Mengato D, Messori A Tags: Haematologica Source Type: research

A t(1;9) translocation involving CSF3R as a novel mechanism in unclassifiable chronic myeloproliferative neoplasm.
;lez-Muñiz S, Balbín M, Puente XS PMID: 28935846 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 21, 2017 Category: Hematology Authors: Gutiérrez-Abril J, Santamaría I, Pitiot AS, Gutiérrez-Fernández A, Alvarez-Eguiluz Á, Vicente JM, Sanzo C, González-Muñiz S, Balbín M, Puente XS Tags: Haematologica Source Type: research