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Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations.
R, Ghia P Abstract Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistiguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations wer...
Source: Haematologica - February 15, 2018 Category: Hematology Authors: Agathangelidis A, Ljungström V, Scarfò L, Fazi C, Gounari M, Pandzic T, Sutton LA, Stamatopoulos K, Tonon G, Rosenquist R, Ghia P Tags: Haematologica Source Type: research

MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia.
Abstract Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents. We knocked down MSH6 in mismatch repair proficient cell lines (697 and UOCB1) and ...
Source: Haematologica - February 15, 2018 Category: Hematology Authors: Evensen NA, Madhusoodhan PP, Meyer J, Saliba J, Chowdhury A, Araten DJ, Nersting J, Bhatla T, Vincent TL, Teachey D, Hunger SP, Yang J, Schmiegelow K, Carroll WL Tags: Haematologica Source Type: research

Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene caused by parental gonosomal mosaicism.
PMID: 29449435 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 15, 2018 Category: Hematology Authors: Wang X, Shen N, Huang M, Lu Y, Hu Q Tags: Haematologica Source Type: research

Mixed-species RNAseq analysis of human lymphoma cells adhering to mouse stromal cells identifies a core gene set that is also differentially expressed in the lymph node microenvironment of mantle cell lymphoma and chronic lymphocytic leukemia patients.
Abstract A subset of hematological cancer patients is refractory to treatment or suffers relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Using RNA sequencing and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell ly...
Source: Haematologica - February 15, 2018 Category: Hematology Authors: Arvidsson G, Henriksson J, Sander B, Wright AP Tags: Haematologica Source Type: research

Dynamic clonal progression in xenografts of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21.
Abstract Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the ...
Source: Haematologica - February 15, 2018 Category: Hematology Authors: Sinclair PB, Blair HH, Ryan SL, Buechler L, Cheng J, Clayton J, Hanna R, Hollern S, Hawking Z, Bashton M, Schwab CJ, Jones L, Russell LJ, Marr H, Carey P, Halsey C, Heidenreich O, Moorman AV, Harrison CJ Tags: Haematologica Source Type: research

The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis.
Abstract Systemic mastocytosis is a complex disease defined by abnormal growth and accumulation of neoplastic mast cells in various organs. Most patients exhibit a D816V-mutated variant of KIT, which confers resistance against imatinib. Clinical problems in systemic mastocytosis arise from mediator-related symptoms and/or organ destruction caused by malignant expansion of neoplastic mast cells and/or other myeloid cells in various organ systems. DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase-targets relevant to systemic mastocytosis. We found that DCC...
Source: Haematologica - February 8, 2018 Category: Hematology Authors: Schneeweiss M, Peter B, Bibi S, Eisenwort G, Smiljkovic D, Blatt K, Jawhar M, Berger D, Stefanzl G, Herndlhofer S, Greiner G, Hoermann G, Hadzijusufovic E, Gleixner KV, Bettelheim P, Geissler K, Sperr WR, Reiter A, Arock M, Valent P Tags: Haematologica Source Type: research

A novel variant Glanzmann thrombasthenia due to co-inheritance of a loss- and a gain-of-function mutation of ITGB3: evidence of a dominant effect of gain-of-function mutations.
PMID: 29439184 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 8, 2018 Category: Hematology Authors: Bury L, Zetterberg E, Leinoe EB, Falcinelli E, Marturano A, Manni G, Nurden AT, Gresele P Tags: Haematologica Source Type: research

Extracellular vesicles in the hematopoietic microenvironment.
Abstract Self-renewal and differentiation are defining characteristics of hematopoietic stem and progenitor cells, and their balanced regulation is central to lifelong function of both blood and immune systems. In addition to cell intrinsic programs, hematopoietic stem and progenitor cells fate decisions are subject to extrinsic cues from within the bone marrow microenvironment and systemically. Yet, many of the paracrine and endocrine mediators that shape hematopoietic function remain to be discovered. Extracellular vesicles serve as evolutionarily conserved, constitutive regulators of cell and tissue homeostasis...
Source: Haematologica - February 8, 2018 Category: Hematology Authors: Butler JT, Abdelhamed S, Kurre P Tags: Haematologica Source Type: research

Severe hemolysis and transfusion reactions after treatment with BGB-3111 and PD-1 antibody for Waldenstr öm Macroglobulinemia.
Severe hemolysis and transfusion reactions after treatment with BGB-3111 and PD-1 antibody for Waldenström Macroglobulinemia. Haematologica. 2018 Feb 08;: Authors: Othman J, Verner E, Tam CS, Huang J, Lin L, Hilger J, Trotman J, Gasioroswki R PMID: 29439186 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 8, 2018 Category: Hematology Authors: Othman J, Verner E, Tam CS, Huang J, Lin L, Hilger J, Trotman J, Gasioroswki R Tags: Haematologica Source Type: research

Lethal neonatal bone marrow failure syndrome with multiple congenital abnormalities including limb defects due to a constitutional deletion of 3' MECOM.
s A Abstract "-". PMID: 29439187 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 8, 2018 Category: Hematology Authors: van der Veken LT, Maiburg MC, Groenendaal F, van Gijn ME, Bloem AC, Erpelinck C, Gröschel S, Sanders MA, Delwel R, Bierings MB, Buijs A Tags: Haematologica Source Type: research

Incidence and risk factors for relapses in HIV-associated non-Hodgkin-lymphoma as observed in the German HIV-related lymphoma cohort study.
In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. This data provides further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. The impact of chemotherapy regimen modifications on relapse rate appears to be limited. PMID: 29439188 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 8, 2018 Category: Hematology Authors: Schommers P, Gillor D, Hentrich M, Wyen C, Wolf T, Oette M, Zoufaly A, Wasmuth JC, Bogner JR, Müller M, Esser S, Schleicher A, Jensen B, Stoehr A, Behrens G, Schultze A, Siehl J, Thoden J, Taylor N, Hoffmann C Tags: Haematologica Source Type: research

Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease.
PMID: 29419424 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Hanudel MR, Rappaport M, Chua K, Gabayan V, Qiao B, Jung G, Salusky IB, Ganz T, Nemeth E Tags: Haematologica Source Type: research

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34+ hematopoietic progenitor cells in patients with sickle cell disease: interim results.
Abstract Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cell harvest for transduction or gene editing. We therefore performed a Phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and 10 were on hydroxyurea. Of 8 patients achieving a CD34+ cell concentration>30 cells/μl, 6 were on hydroxyurea. There was no clear dose response to increasing plerixafor dosage. ...
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Boulad F, Shore T, van Besien K, Minniti C, Barbu-Stevanovic M, Wiener Fedus S, Perna F, Greenberg J, Guarneri D, Nandi V, Mauguen A, Yazdanbakhsh K, Sadelain M, Shi PA Tags: Haematologica Source Type: research

Heterozygous carriers of germline c.657_661del5 founder mutation in NBN gene are at risk of central nervous system relapse of B-cell precursor acute lymphoblastic leukemia.
ic Leukemia/Lymphoma Study Group (PPLLSG) PMID: 29419426 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Tomasik B, Pastorczak A, Fendler W, Bartlomiejczyk M, Braun M, Mycko M, Madzio J, Polakowska E, Ulińska E, Matysiak M, Derwich K, Lejman M, Kowalczyk J, Badowska W, Kazanowska B, Szczepański T, Styczyński J, Irga-Jaworska N, Młynarski W, Polish Pediat Tags: Haematologica Source Type: research

A defined culture method enabling the establishment of ring sideroblasts from induced pluripotent cells of X-linked sideroblastic anemia.
PMID: 29419427 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Hatta S, Fujiwara T, Yamamoto T, Saito K, Kamata M, Tamai Y, Kawamata S, Harigae H Tags: Haematologica Source Type: research

Ibrutinib for chronic lymphocytic leukemia: international experience from a named patient program.
PMID: 29419428 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Hillmen P, Diels J, Healy N, Iraqi W, Aschan J, Wildgust M Tags: Haematologica Source Type: research

Toxicities and outcomes of 621 ibrutinib-treated chronic lymphocytic leukemia patients in the United States: a real-world analysis.
We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. 621 ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, p=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, p=0.8). With a median follow-up of 17 months, an estimated 42% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common...
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Mato AR, Nabhan C, Thompson MC, Lamanna N, Brander DM, Hill B, Howlett C, Skarbnik A, Cheson BD, Zent C, Pu J, Kiselev P, Goy A, Claxton D, Isaack K, Kennard KH, Timlin C, Landsburg D, Winter A, Nasta SD, Bachow SH, Schuster SJ, Dorsey C, Svoboda J, Barr Tags: Haematologica Source Type: research

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels.
i K Abstract This is a letter to the editors. PMID: 29419430 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Yadav P, Merz M, Mai EK, Försti A, Jauch A, Goldschmidt H, Hemminki K Tags: Haematologica Source Type: research

Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma.
We present a case of a pediatric patient with multiply relapsed advanced stage DLBCL who developed sequential antigen loss disease following sequential CAR immunotherapy. This case provides a proof of concept of antigen loss as a mechanism for relapse following immunotherapy in lymphomas, and highlights the need for repeat biopsy and flow cytometric analysis in guiding sequential immunotherapeutic interventions. PMID: 29419431 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES, Lee DW, Shern JF, Fry TJ, Shah NN Tags: Haematologica Source Type: research

The contribution of platelet glycoprotein receptors to inflammatory bleeding prevention is stimulus and organ dependent.
te; B Abstract "-". PMID: 29419432 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Rayes J, Jadoui S, Lax S, Gros A, Wichaiyo S, Ollivier V, Denis CV, Ware J, Nieswandt B, Jandrot-Perrus M, Watson SP, Ho-Tin-Noé B Tags: Haematologica Source Type: research

Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: A study from the Chronic Malignancies Working Party of the EBMT.
A, Garderet L, Kröger N Abstract We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received upfront single (n = 3391) or tandem transplantation (n = 353) between 2005 and 2014 with available data on extramedullary in-volvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n = 682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involveme...
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Gagelmann N, Eikema DJ, Iacobelli S, Koster L, Nahi H, Stoppa AM, Masszi T, Caillot D, Lenhoff S, Udvardy M, Crawley C, Arcese W, Mariette C, Hunter A, Leleu X, Schipperus M, Delforge M, Pioltelli P, Snowden JA, Itälä-Remes M, Musso M, van Biezen A, Gar Tags: Haematologica Source Type: research

Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor V β oligoclonality and CDR3 homology in acquired aplastic anemia.
Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vβ oligoclonality and CDR3 homology in acquired aplastic anemia. Haematologica. 2018 Feb 01;: Authors: Giudice V, Feng X, Lin Z, Hu W, Zhang F, Qiao W, Fernandez Ibanez MDP, Rios O, Young NS Abstract Oligoclonal expansion of CD8+CD28- lymphocytes has been considered indirect evidence for a pathogenic immune response in acquired aplastic anemia. A subset of CD8+CD28- cells with CD57 expression termed effector memory cells is expanded in several immune mediated disea...
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Giudice V, Feng X, Lin Z, Hu W, Zhang F, Qiao W, Fernandez Ibanez MDP, Rios O, Young NS Tags: Haematologica Source Type: research

Outcomes of a large cohort of individuals with clinically ascertained high-count monoclonal B-cell lymphocytosis.
Abstract none. PMID: 29419435 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Parikh SA, Chaffee KG, Larson MC, Hampel PJ, Call TG, Ding W, Kenderian SS, Leis JF, Chanan-Khan AA, Conte MJ, Bowen D, Schwager SM, Slager SL, Hanson CA, Kay NE, Shanafelt TD Tags: Haematologica Source Type: research

Trametinib inhibits RAS-mutant MLL-rearranged acute lymphoblastic leukemia at specific niche sites and reduces ERK phosphorylation in vivo.
PMID: 29419436 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Kerstjens M, Pinhancos SS, Garrido Castro P, Schneider P, Wander P, Pieters R, Stam RW Tags: Haematologica Source Type: research

Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study.
d V Abstract MABLE (NCT01056510) investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every 4 weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondar...
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Michallet AS, Aktan M, Hiddemann W, Ilhan O, Johansson P, Laribi K, Meddeb B, Moreno C, Raposo J, Schuh A, Ünal A, Widenius T, Bernhardt A, Kellershohn K, Messeri D, Osborne S, Leblond V Tags: Haematologica Source Type: research

Clonal evolution in the transition from cutaneous disease to acute leukaemia suggested by liquid biopsy in blastic plasmacytoid dendritic cell neoplasm.
PMID: 29419438 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Ladikou E, Ottolini B, Nawaz N, Allchin RL, Payne D, Ali H, Marafioti T, Shaw J, Ahearne MJ, Wagner SD Tags: Haematologica Source Type: research

Allogeneic stem cell transplantation for FLT3 mutated acute myeloid leukemia in first complete remission: does age really matter?
PMID: 29386373 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Ciurea SO Tags: Haematologica Source Type: research

Large granular lymphocyte cells and immune dysregulation diseases - the chicken or the egg?
PMID: 29386374 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Langerak AW, Assmann JLJC Tags: Haematologica Source Type: research

Hemophilia A: different phenotypes may be explained by multiple and variable effects of the causative mutation in the F8 gene.
PMID: 29386375 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Castaman G Tags: Haematologica Source Type: research

Remembering Professor Felice Gavosto (February 16, 1921 - December 11, 2017).
PMID: 29386376 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - February 1, 2018 Category: Hematology Authors: Gavosto F Tags: Haematologica Source Type: research

Iron overload in transfusion-dependent survivors of hemoglobin Bart's hydrops fetalis.
PMID: 29371322 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 25, 2018 Category: Hematology Authors: Amid A, Chen S, Athale U, Charpentier K, Merelles-Pulcini M, Odame I, Kirby-Allen M Tags: Haematologica Source Type: research

IGVH segment utilization in immunoglobulin gene rearrangement differentiates patients with anti-MAG neuropathy from others IgM-gammopathies.
PMID: 29371323 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 25, 2018 Category: Hematology Authors: Allain JS, Thonier F, Pihan M, Boulland ML, De Guibert S, Launay V, Doncker AV, Ganard M, Aliouat A, Pangault C, Houot R, De Tayrac M, Lamy T, Roussel M, Fest T, Decaux O, Pastoret C Tags: Haematologica Source Type: research

Outcomes of patients with relapsed aggressive adult T-cell leukemia-lymphoma: clinical effectiveness of anti-CCR4 antibody and allogeneic hematopoietic stem cell transplantation.
PMID: 29371324 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 25, 2018 Category: Hematology Authors: Fuji S, Utsunomiya A, Inoue Y, Miyagi T, Owatari S, Sawayama Y, Moriuchi Y, Choi I, Shindo T, Yoshida SI, Yamasaki S, Yamaguchi T, Fukuda T Tags: Haematologica Source Type: research

A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study).
Abstract The outcomes of patients developing major bleeding on oral anticoagulants remain largely unquantified. Objectives are to: 1) describe the burden of major haemorrhage associated with all available oral anticoagulants in terms of: proportion of bleeds which are intracranial-haemorrhages, in-hospital mortality and duration of hospitalisation following major bleeding; 2) identify risk factors for mortality; 3) compare characteristics of major haemorrhage between warfarin and direct-oral anticoagulants for the subgroup of atrial fibrillation and venous-thromboembolism patients. A multi-centre, three-year prosp...
Source: Haematologica - January 25, 2018 Category: Hematology Authors: Green L, Tan J, Morris JK, Alikhan R, Curry N, Everington T, Mclean R, Saja K, Stanworth S, Tait C, MacCallum P Tags: Haematologica Source Type: research

Leptin-deficient obesity prolongs survival in a murine model of myelodysplastic syndrome.
This study revealed that obesity increases survival in animals with myelodysplastic syndrome. This may be due to the greater fat mass of Ob/Ob mice, which acts as a sink for myeloid cells, preventing their accumulation in other key organs such as the liver. PMID: 29371326 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 25, 2018 Category: Hematology Authors: Kraakman MJ, Kammoun HL, Dragoljevic D, Al-Sharea A, Lee MKS, Flynn MC, Stolz CJ, Guirguis AA, Lancaster GI, Chin-Dusting J, Curtis DJ, Murphy AJ Tags: Haematologica Source Type: research

Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: A comparison with controls from the French population.
ier B, Michel G Abstract The prevalence of the metabolic syndrome among adults from the French childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of those patients was compared with that of controls. 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years, female individuals: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III cr...
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Oudin C, Berbis J, Bertrand Y, Vercasson C, Thomas F, Chastagner P, Ducassou S, Kanold J, Tabone MD, Paillard C, Poirée M, Plantaz D, Dalle JH, Gandemer V, Thouvenin S, Sirvent N, Saultier P, Béliard S, Leverger G, Baruchel A, Auquier P, Pannier B, Mich Tags: Haematologica Source Type: research

Partial tandem duplication of KMT2A (MLL) may predict a subset of myelodysplastic syndrome with unique characteristics and poor outcome.
Abstract Partial tandem duplication (PTD) of the KMT2A (MLL) gene is a poor prognostic factor in acute myeloid leukemia, but its significance in the context of myelodysplastic syndrome (MDS) is unknown. Here, we used cytogenomic array to identify MLL-PTD in a group of MDS patients and compared their clinicopathologic characteristics with a cohort of high-risk MDS patients without MLL-PTD. We show that MLL-PTD defines a subset of MDS characterized by high blast count, normal karyotype, and extremely poor prognosis exceeding that of non-MLL-PTD high risk MDS, including those with complex karyotype. Survival of MLL-P...
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Choi SM, Dewar R, Burke PW, Shao L Tags: Haematologica Source Type: research

Venetoclax induced a complete response in a patient with AL amyloidosis plateaued on CyBorD.
eri A PMID: 29351984 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Leung N, Thomé SD, Dispenzieri A Tags: Haematologica Source Type: research

Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft versus host disease: low incidence of lower gastrointestinal tract disease.
Abstract We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received Tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range 22-76). All patients received busulfan-based conditioning, and were transplanted with HLA-matched related or matched unrelated bone marrow or peripheral stem cell grafts. The median follow up for surviving patients was 15 months (range 9-20). The cu...
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Drobyski WR, Szabo A, Zhu F, Keever-Taylor C, Hebert KM, Dunn R, Yim S, Johnson B, D'Souza A, Eapen M, Fenske TS, Hari P, Hamadani M, Horowitz MM, Rizzo JD, Saber W, Shah N, Shaw B, Pasquini M Tags: Haematologica Source Type: research

Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.
ser F Abstract JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27.3%) received at least 6 cycles of ruxolitin...
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Van den Neste E, André M, Gastinne T, Stamatoullas A, Haioun C, Belhabri A, Reman O, Casasnovas O, Guesquieres H, Verhoef G, Claessen MJ, Poirel HA, Copin MC, Dubois R, Vandenberghe P, Stoian IA, Cottereau AS, Bailly S, Knoops L, Morschhauser F Tags: Haematologica Source Type: research

CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.
Medical Research Council Development Grant, Cancer Institute NSW Translationl Program Grant Abstract Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was ...
Source: Haematologica - January 19, 2018 Category: Hematology Authors: Li Z, Ju X, Lee K, Clarke C, Hsu JL, Abadir E, Bryant CE, Pears S, Sunderland N, Heffernan S, Hennessy A, Lo TH, Pietersz GA, Kupresanin F, Fromm PD, Silveira PA, Tsonis C, Cooper WA, Cunningham I, Brown C, Clark GJ, Hart DNJ, Australia National Health an Tags: Haematologica Source Type: research

Association of mutations with morphologic dysplasia in de novo acute myeloid leukemia without 2016 WHO Classification-defined cytogenetic abnormalities.
In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies. We found that cohesin pathway mutations (q (FDR-adjusted p)=0.046) were associated with a higher degree of megakaryocytic dysplasia and STAG2 mutations were marginally associated with greater myeloid lineage dysplasia (q=0.052). Frequent megakaryocytes with separated nuclear lob...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Weinberg OK, Gibson CJ, Blonquist TM, Neuberg D, Pozdnyakova O, Kuo F, Ebert BL, Hasserjian RP Tags: Haematologica Source Type: research

Macrophage scavenger-receptor SR-AI contributes to the clearance of von Willebrand factor.
ari C Abstract Previously, we identified LDL-receptor related protein-1 on macrophages to mediate shear stress-dependent clearance of von Willebrand factor. In control experiments, however, we observed that von Willebrand factor also binds to macrophages independently of this receptor under static conditions, suggesting the existence of additional clearance-receptors. In search for such receptors, we focused on the macrophage-specific scavenger-receptor SR-AI. Von Willebrand factor displays efficient binding to SR-AI (half-max binding 14+/-5 nM). Binding is calcium-dependent and is inhibited by 72+/-4% in the comb...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Wohner N, Muczynski V, Mohamadi A, Legendre P, Aymé G, Christophe OD, Lenting PJ, Denis CV, Casari C Tags: Haematologica Source Type: research

Modeling Multiple Myeloma-Bone Marrow interactions and response to drugs in a 3D surrogate microenvironment.
Abstract Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electron-microscopic analyses, engaged contacts with stromal cells and endothelial cells. Consi...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Belloni D, Heltai S, Ponzoni M, Villa A, Vergani B, Pecciarini L, Marcatti M, Girlanda S, Tonon G, Ciceri F, Caligaris-Cappio F, Ferrarini M, Ferrero E Tags: Haematologica Source Type: research

Growth factor independence 1b. A key player in the genesis and maintenance of acute myeloid leukaemia and myelodysplastic syndrome.
, Khandanpour C, no Abstract Differentiation of haematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factors function can be the basis of (pre)malignancies such as myelodysplastic syndrome or acute myeloid leukaemia. Growth factor independence 1b is a repressing transcription factor regulating quiescence of hematopoietic stem cellss and differentiation of erythrocytes and platelets. Here, we show that low expression of Growth factor independence 1b in blast cells is associated with an inferior prognosis of myelodysplastic syndrome and acute myeloid leukaem...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Thivakaran A, Botezatu L, Hönes JM, Schütte J, Vassen L, Al-Matary YS, Patnana P, Zeller A, Heuser M, Thol F, Gabdoulline R, Olberding N, Frank D, Suslo M, Köster R, Lennartz K, Görgens A, Giebel B, Opalka B, Dührsen U, Khandanpour C, no Tags: Haematologica Source Type: research

TNF receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.
Seiffert M Abstract Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors and their deprivation has been identified as promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of TNF receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro and aberrantly high expression of this receptor in proliferation centers of patients' lymph nodes. St...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Dürr C, Hanna BS, Schulz A, Lucas F, Zucknick M, Benner A, Clear A, Ohl S, Öztürk S, Zenz T, Stilgenbauer S, Li-Weber M, Krammer PH, Gribben JG, Lichter P, Seiffert M Tags: Haematologica Source Type: research

Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: randomized phase II results.
Abstract A prior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after HLA-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft versus host disease incidence, with promising overall and progression-free survival. We performed an open-label 3-arm 1:1:1 phase II randomized-controlled-trial comparing grade II-IV acute graft versus host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B); and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic tra...
Source: Haematologica - January 11, 2018 Category: Hematology Authors: Koreth J, Kim HT, Lange PB, Poryanda SJ, Reynolds CG, Chamling Rai S, Armand P, Cutler CS, Ho VT, Glotzbecker B, Yusuf R, Nikiforow S, Chen YB, Dey B, McMasters M, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP Tags: Haematologica Source Type: research

Desmopressin in moderate hemophilia A patients: a treatment worth considering.
Abstract Desmopressin increases endogenous factor VIII levels in hemophilia A. Large inter-individual variation in the response to desmopressin is observed. Patients with a lower baseline factor VIII activity tend to show a reduced response. Therefore, desmopressin is less frequently used in moderate hemophilia A patients (baseline factor VIII activity 1-5 international units/deciliter), even though factor VIII levels may rise substantially in some of them. We aim to describe the response to desmopressin in moderate hemophilia A patients and to identify predictors. We selected data on 169 patients with moderate he...
Source: Haematologica - January 5, 2018 Category: Hematology Authors: Loomans JI, Kruip MJHA, Carcao M, Jackson S, van Velzen AS, Peters M, Santagostino E, Platokouki H, Beckers E, Voorberg J, van der Bom JG, Fijnvandraat K Tags: Haematologica Source Type: research

The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells ex vivo but fails to prevent leukemia development in a murine model.
, Moussay E PMID: 29305413 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 5, 2018 Category: Hematology Authors: Wierz M, Pierson S, Chouha N, Désaubry L, François JH, Berchem G, Paggetti J, Moussay E Tags: Haematologica Source Type: research

Rapid hematological responses improve outcomes in patients with very advanced (Stage IIIb) cardiac immunoglobulin light chain amyloidosis.
PMID: 29305414 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - January 5, 2018 Category: Hematology Authors: Manwani R, Foard D, Mahmood S, Sachchithanantham S, Lane T, Quarta C, Youngstein T, Rezk T, Lachmann HJ, Gillmore JD, Fontana M, Whelan C, Hawkins PN, Wechalekar AD Tags: Haematologica Source Type: research