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HLA-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients.
ineos J Abstract The immunomodulatory role of HLA-E in hematopoietic stem cell transplantation (HSCT) has not been yet extensively investigated. To this end we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as NK-alloreactivity mediator on HSCT outcome in an acute leukemia setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both, univariate (53% vs 38%, p=0.002...
Source: Haematologica - September 7, 2017 Category: Hematology Authors: Tsamadou C, Fürst D, Vucinic V, Bunjes D, Neuchel C, Mytilineos D, Gramatzki M, Arnold R, Wagner EM, Einsele H, Müller C, Schrezenmeier H, Mytilineos J Tags: Haematologica Source Type: research

Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis.
Abstract While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Here we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells. Diet-induced met...
Source: Haematologica - September 7, 2017 Category: Hematology Authors: Henry CJ, Nemkov T, Casas-Selves M, Bilousova G, Zaberezhnyy V, Higa KC, Serkova NJ, Hansen KC, D' Alessandro A, DeGregori J Tags: Haematologica Source Type: research

Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children's Oncology Group protocol AAML0531.
Abstract Diagnostic biomarkers can be used to determine relapse risk in acute myeloid leukemia, and certain genetic aberrancies have prognostic relevance. A diagnostic immunophenotypic expression profile, which quantifies the amounts of distinct gene products, not just their presence or absence, was established to improve outcome prediction for patients with acute myeloid leukemia. The immunophenotypic expression profile, which defines each patient's leukemia as a location in 15-dimensional space, was generated for 769 patients enrolled in the Children's Oncology Group AAML0531 protocol. Unsupervised hierarchical ...
Source: Haematologica - September 7, 2017 Category: Hematology Authors: Voigt AP, Eidenschink Brodersen L, Alonzo TA, Gerbing RB, Menssen AJ, Wilson ER, Kahwash S, Raimondi SC, Hirsch BA, Gamis AS, Meshinchi S, Wells DA, Loken MR, Children's Oncology Group Tags: Haematologica Source Type: research

Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: A position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
Abstract Allogeneic blood or marrow hematopoietic cell transplantation continues to be the most potent anti-leukemic treatment for adult patients with standard or high-risk, or chemo-refractory acute myeloid leukemia. Until recently, this procedure was generally limited to those recipients who had an available matched-sibling donor or matched-unrelated donor. Technical advances in graft cell processing and manipulation, control of bidirectional T cell alloreactivity, graft-versus-host disease prophylaxis, and other supportive measures in haploidentical transplantation now enables nearly all patients with acute mye...
Source: Haematologica - September 7, 2017 Category: Hematology Authors: Lee CJ, Savani BN, Mohty M, Labopin M, Ruggeri A, Schmid C, Baron F, Esteve J, Gorin NC, Giebel S, Ciceri F, Nagler A Tags: Haematologica Source Type: research

Modeling mixed-lineage-rearranged leukemia initiation in CD34(+) cells: a "CRISPR" solution.
Modeling mixed-lineage-rearranged leukemia initiation in CD34(+) cells: a "CRISPR" solution. Haematologica. 2017 Sep;102(9):1467-1468 Authors: Torres-Ruiz R, Rodriguez-Perales S, Bueno C, Menendez P PMID: 28860233 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - September 1, 2017 Category: Hematology Authors: Torres-Ruiz R, Rodriguez-Perales S, Bueno C, Menendez P Tags: Haematologica Source Type: research

HIF1A is a critical downstream mediator for hemophagocytic lymphohistiocytosis.
In conclusion, our data reveals that HIF1A signaling is a critical mediator for hemophagocytic lymphohistiocytosis and could be a novel therapeutic target for hemophagocytic lymphohistiocytosis. PMID: 28860338 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Huang R, Hayashi Y, Yan X, Bu J, Wang J, Zhang Y, Zhou Y, Tang Y, Wu L, Xu Z, Liu X, Wang Q, Zhou J, Xiao Z, Bridges JP, Marsh RA, Zhang K, Jordan MB, Li Y, Huang G Tags: Haematologica Source Type: research

Treatment outcome in a population-based 'real-world' cohort of chronic myeloid leukemia patients.
Abstract Real-world evaluations of the efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide population-based chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagnosed between January 2008 and April 2013 in the Netherlands. The registries covered 457 patients; 434 in chronic (95%) and 15 patients (3%) in advanced disease phase. 75% of the patients in chronic phase were treated with imatinib and 25% with a second generatio...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Geelen IGP, Thielen N, Janssen JJWM, Hoogendoorn M, Roosma TJA, Willemsen SP, Visser O, Cornelissen JJ, Westerweel PE Tags: Haematologica Source Type: research

Impact of hospital experience on the quality of tyrosine kinase inhibitor response monitoring and consequence for chronic myeloid leukemia patient survival.
PMID: 28860340 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Geelen IGP, Thielen N, Janssen JJWM, Hoogendoorn M, Roosma TJA, Willemsen SP, Valk PJM, Visser O, Cornelissen JJ, Westerweel PE Tags: Haematologica Source Type: research

Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-kB inhibitor.
Abstract IT-901 is a novel and selective NF-kB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells with IT-901 effectively interrupts NF-kB transcriptional activity. Chronic lymphocytic leukemia cells exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation and ATP production and activate intrinsic apoptosis. Inhibition of NF-kB signaling in stromal and myeloid cells, both tumor-supportive elements, fails to induce apoptosis, but impairs NF-kB-driven expression of mo...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Vaisitti T, Gaudino F, Ouk S, Moscvin M, Vitale N, Serra S, Arruga F, Zakrzewski JL, Liou HC, Allan JN, Furman RR, Deaglio S Tags: Haematologica Source Type: research

CUDC-907 in relapsed/refractory diffuse Large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase 1 trial.
In this report the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma are presented, with a particular focus on those with MYC-altered disease. Thirty-seven diffuse large B-cell lymphoma patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently re...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, Parker J, Hafeez A, Tuck D, Younes A Tags: Haematologica Source Type: research

Antigen receptor sequencing of paired bone marrow samples shows homogeneous distribution of acute lymphoblastic leukemia subclones.
Abstract In B-cell precursor acute lymphoblastic leukemia, the initial leukemic cells share the same antigen receptor gene rearrangements. However, due to ongoing rearrangement processes, leukemic cells with different gene rearrangement patterns can develop, resulting in subclone formation. We studied leukemic subclones and their distribution in the bone marrow and peripheral blood at diagnosis. Antigen receptor gene rearrangements (IGH, IGK, TRG, TRD, TRB) were analyzed by next-generation sequencing in seven paired bone marrow samples and five paired bone marrow-blood samples. Background-thresholds were defined, ...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Theunissen PMJ, van Zessen D, Stubbs AP, Faham M, Zwaan M, van Dongen JJM, Van der Velden VHJ Tags: Haematologica Source Type: research

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
nquist B, Mateos MV, Gutiérrez NC, Díaz-Rodriguez E, Garayoa M, Ocio EM Abstract Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor if this proteins, has demonstrated activity in heavily pretreated multiple myeloma patients. The aim of this work was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Hernández-García S, San-Segundo L, González-Méndez L, Corchete LA, Misiewicz-Krzeminska I, Martín-Sánchez M, López-Iglesias AA, Algarín EM, Mogollón P, Díaz-Tejedor A, Paíno T, Tunquist B, Mateos MV, Gutiérrez NC, Díaz-Rodriguez E, Garayoa M, Tags: Haematologica Source Type: research

Concurrent diagnosis of CRLF2-rearranged and Ph+ acute lymphoblastic leukemia: a report of four patients.
PMID: 28860345 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Jain N, Lu X, Daver N, Thakral B, Wang SA, Konoplev S, Patel K, Kanagal-Shamanna R, Valentine M, Tang G, Pemmaraju N, Jorgensen J, Kebriaei P, Nunez CA, Wierda W, Jabbour E, Roberts KG, Mullighan CG, Kantarjian H, Konopleva M Tags: Haematologica Source Type: research

SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia.
Abstract Although small molecule inhibitors of B-cell receptor-associated kinases revolutionized therapy in chronic lymphocytic leukemia, they provide for incomplete responses. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B-cells resident in the protective lymphoid niches. BAFF is critical in survival of both healthy and neoplastic B-cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activati...
Source: Haematologica - August 24, 2017 Category: Hematology Authors: Paiva C, Rowland TA, Sreekantham B, Godbersen C, Best SR, Kaur P, Loriaux MM, Spurgeon SEF, Danilova OV, Danilov AV Tags: Haematologica Source Type: research

The role of constitutive activation of FMS-related tyrosine kinase-3 and NRas/KRas mutational status in infants with KMT2A-rearranged acute lymphoblastic leukemia.
hewe DM PMID: 28838992 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 24, 2017 Category: Hematology Authors: Fedders H, Alsadeq A, Schmäh J, Vogiatzi F, Zimmermann M, Möricke A, Lenk L, Zur Stadt U, Horstmann MA, Pieters R, Schrappe M, Stanulla M, Cario G, Schewe DM Tags: Haematologica Source Type: research

Prognostic discrimination based on the EUTOS long term survival score within the international registry for chronic myeloid leukemia in children and adolescents.
l A Abstract The EUTOS Long Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range 1 month to 6 years) progression and/or death (whichever came first) occurred in 23 patients. For the entire cohort of patients the 5 year progression free survival was 92% (95% CI: 87%-94%) and 5 year survival accounting for chronic myeloid leukemia death was 97% (95% CI: 94%-99%). Of the 309 patients allocated to low (n=199), intermediate (n...
Source: Haematologica - August 24, 2017 Category: Hematology Authors: Millot F, Guilhot J, Suttorp M, Maral Güneş A, Sedlacek P, De Bont E, Li CK, Kalwak K, Lausen B, Culic S, Dworzark M, Kaiserova E, De Moerloose B, Roula F, Biondi A, Baruchel A Tags: Haematologica Source Type: research

The BTK inhibitor CC-292 shows activity in mantle cell lymphoma and synergizes with lenalidomide and NIK inhibitors depending on the NF- κB mutational status.
The BTK inhibitor CC-292 shows activity in mantle cell lymphoma and synergizes with lenalidomide and NIK inhibitors depending on the NF-κB mutational status. Haematologica. 2017 Aug 24;: Authors: Vidal-Crespo A, Rodriguez V, Matas-Céspedes A, Lee E, Rivas-Delgado A, Giné E, Navarro A, Beà S, Campo E, López-Guillermo A, López-Guerra M, Roué G, Colomer D, Pérez-Galán P PMID: 28838994 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 24, 2017 Category: Hematology Authors: Vidal-Crespo A, Rodriguez V, Matas-Céspedes A, Lee E, Rivas-Delgado A, Giné E, Navarro A, Beà S, Campo E, López-Guillermo A, López-Guerra M, Roué G, Colomer D, Pérez-Galán P Tags: Haematologica Source Type: research

Mass spectrometry-based identification of a naturally presented receptor tyrosine kinase-like orphan receptor 1-derived epitope recognized by CD8+ cytotoxic T cells.
ig J, Schmitz M PMID: 28838995 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 24, 2017 Category: Hematology Authors: Heidenreich F, Rücker-Braun E, Walz JS, Eugster A, Kühn D, Dietz S, Nelde A, Tunger A, Wehner R, Link CS, Middeke JM, Stölzel F, Tonn T, Stevanovic S, Rammensee HG, Bonifacio E, Bachmann M, Zeis M, Ehninger G, Bornhäuser M, Schetelig J, Schmitz M Tags: Haematologica Source Type: research

Erythropoietin stimulates murine and human Fibroblast growth factor-23, revealing novel roles for bone and bone marrow.
PMID: 28818868 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 17, 2017 Category: Hematology Authors: Clinkenbeard EL, Hanudel MR, Stayrook KR, Appaiah HN, Farrow EG, Cass TA, Summers LJ, Ip CS, Hum JM, Thomas JC, Ivan M, Richine BM, Chan RJ, Clemens TL, Schipani E, Sabbagh Y, Xu L, Srour EF, Alvarez MB, Kacena MA, Salusky IB, Ganz T, Nemeth E, White KE Tags: Haematologica Source Type: research

Clinical risks and healthcare utilization of haematopoietic cell transplantation for sickle cell disease in the U.S. using merged databases.
del-Azim H, Aljurf M, Olsson RF, Joshi S, Buchbinder D, Eckrich MJ, Hashmi S, Lazarus H, Marks DI, Steinberg A, Saad A, Gergis U, Krishnamurti L, Abraham A, Rangarajan HG, Walters M, Lipscomb J, Saber W, Satwani P Abstract Allogeneic hematopoietic cell transplant advances for sickle cell disease improve outcomes, but limited healthcare utilization analysis exists. We hypothesized that early transplant (age
Source: Haematologica - August 17, 2017 Category: Hematology Authors: Arnold SD, Brazauskas R, He N, Li Y, Aplenc R, Jin Z, Hall M, Atsuta Y, Dalal J, Hahn T, Khera N, Bonfim C, Majhail NS, Diaz MA, Freytes CO, Wood WA, Savani BM, Kamble RT, Parsons S, Ahmed I, Sullivan K, Beattie S, Dandoy C, Munker R, Marino S, Bitan M, A Tags: Haematologica Source Type: research

Consolidation treatment with lenalidomide following front-line or salvage chemoimmunotherapy in chronic lymphocytic leukemia.
PMID: 28798068 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 10, 2017 Category: Hematology Authors: Strati P, Keating MJ, Burger JA, O'Brien SM, Wierda WG, Estrov Z, Zacharian G, Ferrajoli A Tags: Haematologica Source Type: research

MLL-TET1 fusion protein promotes immortalization of myeloid progenitor cells and leukemia development.
PMID: 28798069 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 10, 2017 Category: Hematology Authors: Kim HS, Oh SH, Kim JH, Kim JY, Kim DH, Lee SJ, Choi SU, Park KM, Ryoo ZY, Park TS, Lee S Tags: Haematologica Source Type: research

CXCL13 levels are elevated in patients with Waldenstrom's Macroglobulinemia, and are predictive of major response to ibrutinib.
PMID: 28798070 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 10, 2017 Category: Hematology Authors: Vos JM, Tsakmaklis N, Patterson CJ, Meid K, Castillo JJ, Brodsky P, Ganz T, Pals ST, Kersten MJ, Xu L, Yang G, Treon SP, Hunter ZR Tags: Haematologica Source Type: research

Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.
re F Abstract Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematological malignancy with a poor prognosis. No consensus for optimal treatment modalities is available today. Targeting the NF-κB pathway is considered as a promising approach since blastic plasmacytoid dendritic cell neoplasm have been reported to exhibit a constitutive activation of the NF-κB pathway. Moreover, NF-κB inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib interferes in vitro with leukemic cell prolife...
Source: Haematologica - August 10, 2017 Category: Hematology Authors: Philippe L, Ceroi A, Bôle-Richard E, Jenvrin A, Biichle S, Perrin S, Limat S, Bonnefoy F, Deconinck E, Saas P, Garnache-Ottou F, Angelot-Delettre F Tags: Haematologica Source Type: research

Endotoxemia shifts neutrophils with TIMP-free gelatinase B/ MMP-9 from bone marrow to periphery and induces systematic upregulation of TIMP-1.
Abstract Lipopolysaccharides or endotoxins elicit an excessive host inflammatory response and lead to life-threatening conditions such as endotoxemia and septic shock. Lipopolysaccharides trigger mobilization and stimulation of leukocytes and exaggerated production of pro-inflammatory molecules including cytokines and proteolytic enzymes. Matrix metalloproteinase-9 (MMP-9) or gelatinase B, a protease stored in the tertiary granules of polymorphonuclear leukocytes, has been implicated in such inflammatory reactions. Moreover, several studies even pinpointed MMP-9 as a potential target molecule to counter excessive ...
Source: Haematologica - August 3, 2017 Category: Hematology Authors: Vandooren J, Swinnen W, Ugarte-Berzal E, Boon L, Dorst D, Martens E, Opdenakker G Tags: Haematologica Source Type: research

Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk.
Abstract The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Yet, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Whereas numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment by engaging in several cross-talk mechanisms. In this review, we describe how chronic lymphocytic leukemia cell...
Source: Haematologica - August 3, 2017 Category: Hematology Authors: van Attekum MH, Eldering E, Kater AP Tags: Haematologica Source Type: research

Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach.
Abstract The use of novel B cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenstroms macroglobulinemia. Ibrutinib, the first-in-class inhibitor or Bruton's tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ have recently been approved for several indolent B cell malignancies. These drugs especially foresee in previously unmet needs for patients with relapsed or refractory diseas...
Source: Haematologica - August 3, 2017 Category: Hematology Authors: de Weerdt I, Koopmans SM, Kater AP, van Gelder M Tags: Haematologica Source Type: research

Pseudo-monoclonal gammopathy: a report of four cases.
PMID: 28775120 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 3, 2017 Category: Hematology Authors: Jawad MD, Go RS, Witzig TE, Mikhael JR, Ravindran A, Murray DL Tags: Haematologica Source Type: research

Italian real life experience with brentuximab vedotin: results of a large observational study on 40 relapsed/refractory systemic anaplastic large cell lymphoma.
P, Liberati AM, Pinto A, Pavone V, Gherlinzoni F, Naso V, Volpetti S, Trentin L, Goldaniga MC, Bonfichi M, De Renzo A, Schiavotto C, Spina M, Storti S, Carella AM, Stefoni V, Argnani L, Zinzani PL Abstract From November 2012 to July 2014, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context according to the national law 648/96. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in the everyday clinical practice to check if clinical trial results are confirmed even in a real life...
Source: Haematologica - August 3, 2017 Category: Hematology Authors: Broccoli A, Pellegrini C, Di Rocco A, Puccini B, Patti C, Gini G, Mannina D, Tani M, Rusconi C, Romano A, Vanazzi A, Botto B, Carlo-Stella C, Hohaus S, Musto P, Mazza P, Molica S, Corradini P, Fama A, Gaudio F, Merli M, Gravetti A, Gritti G, Arcari A, Tos Tags: Haematologica Source Type: research

Circulating microRNA expressions can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma.
PMID: 28775122 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 3, 2017 Category: Hematology Authors: Jung SH, Lee SE, Lee M, Kim SH, Yim SH, Kim TW, Min CK, Chung YJ Tags: Haematologica Source Type: research

TLR9 stimulation can induce IkappaBzeta expression and IgM secretion in chronic lymphocytic leukemia cells.
We report that, while CpG induces NFKBIZ mRNA in all the samples analyzed, it induces the IkappaBzeta protein in a selected group of cases, through an unanticipated post-transcriptional mechanism. Interestingly, IkappaBzeta plays a causal role in sustaining CpG-induced cell viability and chemoresistance, and CpG stimulation can unleash immunoglobulin secretion by IkappaBzeta-positive malignant cells. These results identify and characterize IkappaBzeta as a marker and effector molecule of distinct key pathways in chronic lymphocytic leukemia. PMID: 28775123 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - August 3, 2017 Category: Hematology Authors: Fonte E, Vilia MG, Reverberi D, Sana I, Scarfò L, Ranghetti P, Orfanelli U, Cenci S, Cutrona G, Ghia P, Muzio M Tags: Haematologica Source Type: research

p27 in FLT3-driven acute myeloid leukemia: many roads lead to ruin.
PMID: 28760806 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - August 1, 2017 Category: Hematology Authors: Uras IZ, Bellutti F, Sexl V Tags: Haematologica Source Type: research

Long non-coding RNAs: another brick in the wall of normal karyotype acute myeloid leukemia?
PMID: 28760807 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - August 1, 2017 Category: Hematology Authors: Medeiros BC Tags: Haematologica Source Type: research

ARID1A mutation in blastic plasmacytoid dendritic cell neoplasm.
PMID: 28751556 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Wang L, Yang M, Zhang X, Yang C, Huang X, Wang Z, Jin J Tags: Haematologica Source Type: research

The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling.
Bladé J, Roué G, Fernández de Larrea C Abstract Most of patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequently reduction on IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinatorial effect of a MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of BET br...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Díaz T, Rodríguez V, Lozano E, Mena MP, Calderón M, Rosiñol L, Martínez A, Tovar N, Pérez-Galán P, Bladé J, Roué G, Fernández de Larrea C Tags: Haematologica Source Type: research

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.
ildgust M, Mahler M, Burger JA Abstract The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize atrial fibrillation with ibrutinib and its management. Atrial fibrillation incidence was 6.5% (95% CI: 4.8, 8.5) for ibrutinib at 16.6-months (vs. 1.6% [95% CI: 0.8, 2.8] for comparator) and 10.4% (95% CI: 8.4, 12.9) at 36-mont...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Brown JR, Moslehi J, O' Brien S, Ghia P, Hillmen P, Cymbalista F, Shanafelt TD, Fraser G, Rule S, Kipps TJ, Coutre S, Dilhuydy MS, Cramer P, Tedeschi A, Jaeger U, Dreyling M, Byrd JC, Howes A, Todd M, Vermeulen J, James DF, Clow F, Styles L, Valentino R, Tags: Haematologica Source Type: research

Loss-of-function but not dominant-negative intragenic IKZF1 deletions are associated with an adverse prognosis in adult BCR-ABL-negative acute lymphoblastic leukemia.
urmeister T Abstract Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia (ALL). Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniforml...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Kobitzsch B, Gökbuget N, Schwartz S, Reinhardt R, Brüggemann M, Viardot A, Wäsch R, Starck M, Thiel E, Hoelzer D, Burmeister T Tags: Haematologica Source Type: research

Mutational Status of IGHV is the most reliable prognostic Marker in Trisomy 12 Chronic Lymphocytic Leukemia.
i V PMID: 28751560 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Bulian P, Bomben R, Dal Bo M, Zucchetto A, Rossi FM, Degan M, Pozzo F, Bittolo T, Bravin V, D'Agaro T, Cerri M, Chiarenza A, Chaffee KG, Condoluci A, D'Arena G, Spina M, Zaja F, Pozzato G, Di Raimondo F, Rossi D, Del Poeta G, Gaidano G, Shanafelt TD, Gatt Tags: Haematologica Source Type: research

Exome sequencing identifies recurrent BCOR gene alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.
hen A Abstract Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse red pulp lymphoma cases from paired tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse red pulp lymphoma samples and compared to those ide...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Jallades L, Baseggio L, Sujobert P, Huet S, Chabane K, Callet-Bauchu E, Verney A, Hayette S, Desvignes JP, Salgado D, Levy N, Béroud C, Felman P, Berger F, Magaud JP, Genestier L, Salles G, Traverse-Glehen A Tags: Haematologica Source Type: research

Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1.
Abstract Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safety were evaluated in subgroups defined according to type (proteasome inhibitor [PI] and immunomodulatory drug) and number (1 vs 2 or 3) of prior therapies received. Of 722 patients, 503 (70%) had received a prior ...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Mateos MV, Masszi T, Grzasko N, Hansson M, Sandhu I, Pour L, Viterbo L, Jackson SR, Stoppa AM, Gimsing P, Hamadani M, Borsaru G, Berg D, Lin J, Di Bacco A, van de Velde H, Richardson PG, Moreau P Tags: Haematologica Source Type: research

Calreticulin as a novel B cell receptor antigen in chronic lymphocytic leukemia.
PMID: 28751563 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Ten Hacken E, Gounari M, Back JW, Shimanovskaya E, Scarfo L, Kim E, Burks J, Ponzoni M, Ramirez GA, Wierda WG, Estrov Z, Keating MJ, Ferrajoli A, Stamatopoulos K, Ghia P, Burger JA Tags: Haematologica Source Type: research

Increase of von Willebrand Factor with ageing in type 1 Von Willebrand disease: fact or fiction?
PMID: 28751564 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Borghi M, Guglielmini G, Mezzasoma AM, Falcinelli E, Bury L, Malvestiti M, Gresele P Tags: Haematologica Source Type: research

Incidence and outcome of acquired aplastic anemia-real-world data from patients diagnosed in Sweden from 2000-2011.
In conclusion, younger aplastic anemia patients experience a very good long-term survival, while especially that of patients ≥60 years remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients and prospective studies to address this medical need are warranted. PMID: 28751565 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Vaht K, Göransson M, Carlson K, Isaksson C, Lenhoff S, Sandstedt A, Uggla B, Winiarski J, Ljungman P, Brune M, Andersson PO Tags: Haematologica Source Type: research

Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951.
oit Y Abstract Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma. The value of asparaginase was further addressed in a group of non-very high risk patients by comparing a prolonged (long-asparaginase) versus standard (short-asparaginase) native E.coli asparaginase treatment through a randomized question as part of the phase III 58951 trial of the European Organisation for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poirée M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cave' H, Rohrlich P, Bertrand Y, Benoit Y Tags: Haematologica Source Type: research

The ADAMTS13(1239-1253) peptide is a dominant HLA-DR1-restricted CD4+ T-cell epitope.
zes S Abstract Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against "A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. The implication of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13. Candidate T-cell epitopes were predicted in silico and bindin...
Source: Haematologica - July 27, 2017 Category: Hematology Authors: Gilardin L, Delignat S, Peyron I, Ing M, Lone YC, Gangadharan B, Michard B, Kherabi Y, Sharma M, Pashov A, Latouche JB, Hamieh M, Toutirais O, Loiseau P, Galicier L, Veyradier A, Kaveri S, Maillère B, Coppo P, Lacroix-Desmazes S Tags: Haematologica Source Type: research

Notch2 blockade enhances hematopoietic stem cell mobilization and homing.
Abstract Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation may mobilize limited numbers of hematopoietic progenitor cells into blood, precluding use of the procedure, or being placed at increased risk for complications due to slow hematopoietic reconstitution. Developing more efficacious hematopoietic progenitor cell mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is dispensable for homeostasis of adult hematopoietic stem cells, Notch-ligand adhesive interaction maintains ...
Source: Haematologica - July 20, 2017 Category: Hematology Authors: Wang W, Yu S, Myers J, Wang Y, Xin WW, Alkabri M, Xin AW, Li M, Huang AY, Xin W, Siebel CW, Lazarus HM, Zhou L Tags: Haematologica Source Type: research

Rapamycin is highly effective in murine models of immune-mediated bone marrow failure.
Abstract Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure. Rapamycin ameliorated pancytopenia, improved bone marrow cellularity, and extended animal surviva...
Source: Haematologica - July 20, 2017 Category: Hematology Authors: Feng X, Lin Z, Sun W, Hollinger MK, Desierto MJ, Keyvanfar K, Malide D, Muranski P, Chen J, Young NS Tags: Haematologica Source Type: research

Changes in the incidence and mortality of candidemia in patients with hematological malignancies in the last ten years. SEIFEM 2015-B report.
a M, Fracchiolla NS, Mancini V, Nosari A, Del Principe MI, Aversa F, Tumbarello M PMID: 28729301 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - July 20, 2017 Category: Hematology Authors: Pagano L, Dragonetti G, Cattaneo C, Marchesi F, Veggia B, Busca A, Candoni A, Prezioso L, Criscuolo M, Cesaro S, Delia M, Fanci R, Stanzani M, Ferrari A, Martino B, Melillo L, Nadali G, Simonetti E, Ballanti S, Picardi M, Castagnola C, Decembrino N, Gazzo Tags: Haematologica Source Type: research

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk MDS.
ndi F Abstract Vosaroxin is an anti-cancer quinolone derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥ 60 years of age with newly diagnosed acute myeloid leukemia (AML) (n=58) or myelodysplastic syndrome (MDS) (≥ 10% blasts) (n=7) in a phase 2 non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on Days 1 and 4 with decitabine 20 mg/m2 Days 1-5 every 4-6 weeks for up to 7 cycles. Due to high incidence of mucositis the subsequent 43 patients received vosaroxin 70 mg/m2 Days 1 and 4. Sixty-five patients with median age 69 years (range 60-78), s...
Source: Haematologica - July 20, 2017 Category: Hematology Authors: Daver N, Kantarjian H, Garcia-Manero G, Jabbour E, Borthakur G, Brandt M, Pierce S, Vaughan K, Ning J, Nogueras González GM, Patel K, Jorgensen J, Pemmaraju N, Kadia T, Konopleva M, Andreeff M, DiNardo C, Cortes J, Ward R, Craig A, Ravandi F Tags: Haematologica Source Type: research

Amotosalen/UVA pathogen inactivation technology reduces platelet activatability, induces apoptosis and accelerates clearance.
JH Abstract Amotosalen and ultraviolet A photochemical-based pathogen reduction using the InterceptTM Blood System is an effective and established technology for platelet and plasma components, which is adopted in more than 40 countries worldwide. Several reports point towards a reduced platelet function after Amotosalen/UVA exposure. The current study was undertaken to identify the mechanisms responsible for the early impairment of platelet function by the InterceptTM Blood System. Twenty-five platelet apheresis units were collected from healthy volunteers following standard procedures and split into 2 component...
Source: Haematologica - July 20, 2017 Category: Hematology Authors: Stivala S, Gobbato S, Infanti L, Reiner MF, Bonetti N, Meyer SC, Camici GG, Lüscher TF, Buser A, Beer JH Tags: Haematologica Source Type: research