Haematologica (Haematologica )

Publisher: Ferrata Storti Foundation

Description

Impact factor 5.94

  • 5-year impact
    6.00
  • Cited half-life
    4.80
  • Immediacy index
    1.45
  • Eigenfactor
    0.04
  • Article influence
    2.18
  • Other titles
    Haematologica (Rome, Italy: Online), Haematologica/the hematology journal
  • ISSN
    1592-8721
  • OCLC
    44358058
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • Mercedes Borge, María Belén Almejún, Enrique Podaza, Ana Colado, Horacio Fernández Grecco, María Cabrejo, Raimundo F Bezares, Mirta Giordano, Romina Gamberale
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    ABSTRACT: - Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Rinako Nakagawa, Milica Vukovic, Anuradha Tarafdar, Emilio Cosimo, Karen Dunn, Alison M McCaig, Ailsa Holroyd, Fabienne McClanahan, Alan G Ramsay, John G Gribben, Alison M Michie
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    ABSTRACT: Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in the lymphoid organs. Reduced function of PKCα leads to an upregulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Monique P Gelderman, Jin Hyen Baek, Ayla Yalamanoglu, Michele Puglia, Florence Vallelian, Bo Burla, Jaroslav Vostal, Dominik J Schaer, Paul W Buehler
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    ABSTRACT: Intermediate beta-thalassemia demonstrates a broad spectrum of sequelae and may require occasional blood transfusions over a lifetime to correct anemia. Iron overload in intermediate beta-thalassemia results from a paradoxical intestinal absorption, iron release from macrophages and hepatocytes, and sporadic transfusions. Pathological iron accumulation in parenchyma is caused by chronic exposure to non-transferrin bound iron (NTBI) in plasma. The iron scavenger and transport protein transferrin (Tf) is a potential treatment being studied for correction of anemia. However, Tf may also function to prevent or reduce iron loading of tissues when exposures to NTBI increase. Here we evaluate the effects of apoTf dosing on tissue iron loading and early tissue pathology in non-transfused and transfused Hbbth3/+ mice. The murine Hbbth3/+ phenotype demonstrates mild to moderate anemia and exhibits consistent tissue iron accumulation in the spleen, liver, kidneys and myocardium. Our results confirmed that chronic apoTf administration resulted in normalization of anemia. Furthermore, we demonstrate normalization of tissue iron content in liver, kidney and heart and attenuation of early tissue changes in non-transfused Hbbth3/+ mice. ApoTf treatment was also found to attenuate transfusion mediated increases in plasma NTBI and asscociated excess tissue iron loading. These therapeutic effects were associated with normalization of Tf saturation and suppressed plasma NTBI. ApoTf treatment was found to modulate a fundamental iron regulatory pathway as evidenced by decreased erythroid Fam132b (erythroferrone) expression, increased liver HAMP expression and plasma hepcidin-25 lelvels and consequently reduced intestinal ferroportin-1 in apoTf treated thalassemic mice. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Senthil Raja Jayapal, Chelsia Qiuxia Wang, Xavier Bisteau, Matias J Caldez, Shuhui Lim, Vinay Tergaonkar, Motomi Osato, Philipp Kaldis
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    ABSTRACT: Mouse knockouts of Cdk2 and Cdk4 are individually viable whereas the double knockouts are embryonic lethal due to heart defects and this precludes the investigation of their overlapping roles in definitive hematopoiesis. Here we use a conditional knockout mouse model to investigate the effect of combined loss of Cdk2 and Cdk4 in hematopoietic cells. Cdk2fl/flCdk4-/-vavCre mice are viable but displayed a significant increase in erythrocyte size. Cdk2fl/flCdk4-/-vavCre mouse bone marrow exhibited reduced phosphorylation of the retinoblastoma protein and reduced expression of E2F target genes such as cyclin A2 and Cdk1. Erythroblasts lacking Cdk2 and Cdk4 displayed a lengthened G1 phase due to impaired phosphorylation of the retinoblastoma protein. Deletion of the retinoblastoma protein rescued the increased size displayed by erythrocytes lacking Cdk2 and Cdk4, indicating that the retinoblastoma/Cdk2/Cdk4 pathway regulates erythrocyte size. The recovery of platelet counts following a 5 fluorouracil challenge was delayed in Cdk2fl/flCdk4-/-vavCre mice revealing a critical role for Cdk2 and Cdk4 in stress hematopoiesis. Our data indicates that Cdk2 and Cdk4 play important overlapping roles in homeostatic and stress hematopoiesis, which need to be considered during the use of broad-spectrum cyclin-dependent kinase inhibitors for cancer therapy. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Dimitrios Papaioannou, Anna-Maria Strothmeyer, Marcus Dühren-von Minden, Andrea Keppler-Hafkemeyer, Katja Zirlik, Kristina Mikesch, Cornelis A M van Bergen, Marcelo A Navarrete, Hendrik Veelken
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    ABSTRACT: - Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Jinbo Huang, Meili Ge, Shihong Lu, Jun Shi, Xingxin Li, Jizhou Zhang, Min Wang, Wei Yu, Yingqi Shao, Zhendong Huang, Jing Zhang, Neng Nie, Yizhou Zheng
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    ABSTRACT: - Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An excess of free heme is present in the blood during many types of hemolytic anemia. This has been linked to organ damage caused by heme-mediated oxidative stress and vascular inflammation. We investigated the mechanism of heme-induced coagulation activation in vivo. Heme caused coagulation activation in wild type mice that was attenuated by an anti-tissue factor antibody and in mice expressing low levels of tissue factor. In contrast, neither factor XI deletion nor inhibition of factor XIIa-mediated factor XI activation reduced heme-induced coagulation activation, suggesting that the intrinsic coagulation pathway is not involved. We investigated the source of tissue factor in heme-induced coagulation activation. Heme increased the procoagulant activity of mouse macrophages and human PBMCs. Tissue factor-positive staining was observed on leukocytes isolated from the blood of heme-treated mice but not on endothelial cells in the lungs. Furthermore, heme increased vascular permeability in the mouse lungs, kidney and heart. Deletion of tissue factor from either myeloid cells, hematopoietic and endothelial cells, or inhibition of tissue factor expressed by non-hematopoietic cells did not reduce heme-induced coagulation activation. However, heme-induced activation of coagulation was abolished when both non-hematopoietic and hematopoietic cell tissue factor was inhibited. Finally, we demonstrated that coagulation activation was partially attenuated in sickle cell mice treated with recombinant hemopexin to neutralize free heme. Our results indicate that heme promotes tissue factor-dependent coagulation activation and induces tissue factor expression on leukocytes in vivo. We also demonstrated that free heme may contribute to thrombin generation in a mouse model of sickle cell disease. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: - Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hemoglobin SC disease is a very prevalent hemoglobinopathy, however very little is known specifically about this condition. There appears to be an increased risk of thromboembolic events in hemoglobin SC disease, but studies evaluating the hemostatic alterations are lacking. We describe a cross-sectional observational study evaluating coagulation activation markers in adult hemoglobin SC patients, in comparison with sickle cell anemia patients and healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients were in use of hydroxyurea. Hemoglobin SC patients presented a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (p<0.01). Hemoglobin SC patients presented lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (p<0.05). Endothelial activation (soluble thrombomodulin and soluble vascular cell adhesion molecule-1), and inflammation (tumor necrosis factor-alpha) markers were both significantly elevated in hemoglobin SC patients when compared to controls, being as high as the levels seen in sickle cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In summary, our results demonstrate that hemoglobin SC patients present a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Davide Rossi, Alessio Bruscaggin, Piera La Cava, Sara Galimberti, Elena Ciabatti, Stefano Luminari, Luigi Rigacci, Alessandra Tucci, Alessandro Pulsoni, Giovanni Bertoldero, Daniele Vallisa, Chiara Rusconi, Michele Spina, Luca Arcaini, Francesco Angrilli, Caterina Stelitano, Francesco Merli, Gianluca Gaidano, Massimo Federico, Giuseppe A Palumbo
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    ABSTRACT: Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCγ receptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone vs rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone vs rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. Primary endpoint was time-to-treatment-failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence rituximab single agent activity, did not affect time-to-treatment-failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (p=.742, p=.252, respectively). These results were consistent even when the analysis was conducted by intention to treatment arm, indicating that different chemotherapy regimens and loads did not differentially interact with FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time-to-treatment-failure in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (p=.001; q<.1), but not in arms lacking doxorubicin (rituximab-cyclophosphamide-vincristine-prednisone, rituximab-fludarabine-mitoxantrone). The impact of MLH1 on time-to-treatment-failure was independent after adjusting for the Follicular Lymphoma International Prognostic Index and other potential confounding variables by multivariate analysis. These data indicate that MLH1 genotype is a predictor of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone treatment failure in advanced follicular lymphoma and confirm that FCGR2A and FCGR3A polymorphisms have no impact when follicular lymphoma is treated with rituximab plus chemotherapy (clinicaltrials.gov identifier: NCT00774826). Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Carol Moreno, Marco Montillo, Panayiotis Panayiotidis, Maria Dimou, Adrian Bloor, Jehan Dupuis, Anna Schuh, Stefan Norin, Christian Geisler, Peter Hillmen, [......], Martin Rubio, Roberto Marasca, Gerardo Musuraca, Luigi Rigacci, Lucia Farina, Rossella Paolini, Sarka Pospisilova, Eva Kimby, Colm Bradley, Emili Montserrat
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    ABSTRACT: We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. The total number of patients was 103, with a median age of 65 years (range, 39-85). The median number of prior lines of therapy was 4 (range, 1-13), including in most cases rituximab-, fludarabine- and alemtuzumab- based regimens; thirteen patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. The study herein reported is registered as ClinicalTrial.gov National Cancer Institute 01453062. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
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    ABSTRACT: Herein, we phenotypically and functionally characterize a distinct CD56low natural killer cell subset based on CD16 expression levels in bone marrow and peripheral blood of healthy children and pediatric patients with acute lymphoblastic leukemia. Our findings for the first time demonstrate that CD56lowCD16low natural killer cells are more abundant in bone marrow than in peripheral blood and their frequency is further increased in children with acute lymphoblastic leukemia. Bone marrow and peripheral blood CD56lowCD16low natural killer cells compared with CD56lowCD16high natural killer cells express lower levels of killer inhibitory receptors, higher levels of CD27, CD127, CD122, CD25, but undetectable levels of CD57, this finding suggesting that they have a higher proliferative and differentiation potential. Moreover, CD56lowCD16low natural killer cells display higher levels of CXCR4 and undetectable levels of CX3CR1 and, consistently, can be rapidly mobilized in peripheral blood in response to CXCR4 antagonist. Unlike CD56lowCD16high, both bone marrow and peripheral blood CD56lowCD16low natural killer cells release IFNγ following cytokine stimulation, and represent the major cytotoxic natural killer cell population against K562 or acute lymphoblastic leukemia target cells. All these data suggest that CD56lowCD16low natural killer cells are multifunctional cells and that the presence of haematological malignancies affects their frequency and functional ability at both tumor site and in the periphery. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Peter Paschka, Richard F Schlenk, Verena I Gaidzik, Julia K Herzig, Teresa Aulitzky, Lars Bullinger, Daniela Späth, Veronica Teleanu, Andrea Kündgen, Claus-Henning Köhne, [......], Heinz-A Horst, Mark Ringhoffer, Katharina Götze, David Nachbaur, Thomas Kindler, Michael Heuser, Felicitas Thol, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
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    ABSTRACT: We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1 mutations and identified these mutations in 103 (6.1%) patients. ASXL1 mutations were associated with older age (P<.0001), male sex (P=.041), secondary acute myeloid leukemia (P<.0001), and lower values for bone marrow (P<.0001) and circulating (P<.0001) blasts. ASXL1 mutations occurred in all cytogenetic risk-groups; normal karyotype (40%), other intermediate-risk cytogenetics (26%), high (24%) and low-risk (10%) cytogenetics. ASXL1 mutations were associated with RUNX1 (P<.0001) and IDH2R140 mutations (P=.007), whereas there was an inverse correlation with NPM1 (P<.0001), FLT3-ITD (P=.0002), and DNMT3A (P=.02) mutations. ASXL1 mutations were associated with lower complete remission rate (56% vs 74%; P=.0002), and both inferior event-free survival (at 5-years: 15.9% vs 29.0%; P=.02) and overall survival (at 5-years: 30.3% vs 45.7%; P=.0004) compared to wildtype ASXL1. In multivariable analyses, ASXL1 and RUNX1 mutation as single variable had no significant impact on prognosis. However, we observed a significant interaction (P=.04) for these mutations, in that patients with the genotype ASXL1mutated/RUNX1mutated had a higher risk of death (hazard ratio 1.8) compared to patients without this genotype. ASXL1 mutation, particularly in the context of a coexisting RUNX1 mutation, constitutes a strong adverse prognostic factor in acute myeloid leukemia. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 01/2015;
  • Haematologica 01/2015; 100(1):1-3.
  • Haematologica 01/2015; 100(1):e1-e3l.
  • Haematologica 01/2015; 100(1):e41.