Subjects -> MEDICAL SCIENCES (Total: 8196 journals)
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HEMATOLOGY (160 journals)                     

Showing 1 - 151 of 151 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 2)
Acta Haematologica     Full-text available via subscription   (Followers: 23)
Acta Haematologica Polonica     Open Access  
Adipocyte     Open Access  
Advances in Hematology     Open Access   (Followers: 13)
Africa Sanguine     Full-text available via subscription  
American Journal of Hematology     Hybrid Journal   (Followers: 52)
Anemia     Open Access   (Followers: 6)
Annals of Hematology     Hybrid Journal   (Followers: 15)
Archives of Hematology Case Reports and Reviews     Open Access  
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 29)
Artery Research     Hybrid Journal   (Followers: 4)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 4)
ASAIO Journal     Hybrid Journal   (Followers: 2)
Best Practice & Research Clinical Haematology     Hybrid Journal   (Followers: 5)
Blood     Hybrid Journal   (Followers: 291)
Blood Advances     Open Access   (Followers: 6)
Blood and Lymphatic Cancer : Targets and Therapy     Open Access   (Followers: 7)
Blood Cancer Journal     Open Access   (Followers: 18)
Blood Cells, Molecules, and Diseases     Hybrid Journal   (Followers: 8)
Blood Coagulation & Fibrinolysis     Hybrid Journal   (Followers: 60)
Blood Pressure     Open Access  
Blood Pressure Monitoring     Hybrid Journal   (Followers: 1)
Blood Purification     Full-text available via subscription   (Followers: 6)
Blood Reviews     Hybrid Journal   (Followers: 26)
BMC Hematology     Open Access   (Followers: 7)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 29)
Bone Marrow Transplantation     Hybrid Journal   (Followers: 17)
British Journal of Diabetes & Vascular Disease     Open Access   (Followers: 21)
British Journal of Haematology     Hybrid Journal   (Followers: 60)
British Journal of Primary Care Nursing - Cardiovascular Disease, Diabetes and Kidney Care     Full-text available via subscription   (Followers: 10)
Canadian Journal of Diabetes     Hybrid Journal   (Followers: 28)
Case Reports in Hematology     Open Access   (Followers: 10)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32)
Clinical Diabetes     Full-text available via subscription   (Followers: 39)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Lymphoma & Myeloma     Full-text available via subscription   (Followers: 2)
Clinical Lymphoma Myeloma and Leukemia     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1)
Conquest : The Official Journal of Diabetes Australia     Full-text available via subscription   (Followers: 3)
Current Angiogenesis     Hybrid Journal   (Followers: 1)
Current Diabetes Reports     Hybrid Journal   (Followers: 24)
Current Diabetes Reviews     Hybrid Journal   (Followers: 27)
Current Hematologic Malignancy Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Hematology     Hybrid Journal   (Followers: 20)
Cytotherapy     Full-text available via subscription   (Followers: 2)
Der Diabetologe     Hybrid Journal   (Followers: 2)
Diabetes     Full-text available via subscription   (Followers: 404)
Diabetes aktuell     Hybrid Journal   (Followers: 3)
Diabetes and Vascular Disease Research     Hybrid Journal   (Followers: 20)
Diabetes Care     Full-text available via subscription   (Followers: 462)
Diabetes Case Reports     Open Access  
Diabetes Educator     Hybrid Journal   (Followers: 27)
Diabetes Management     Full-text available via subscription   (Followers: 15)
Diabetes Research and Clinical Practice     Hybrid Journal   (Followers: 71)
Diabetes Spectrum     Full-text available via subscription   (Followers: 16)
Diabetes Technology & Therapeutics     Hybrid Journal   (Followers: 50)
Diabetes Therapy     Open Access   (Followers: 23)
Diabetic Foot & Ankle     Open Access   (Followers: 10)
Diabetic Medicine     Hybrid Journal   (Followers: 144)
Diabetologia     Hybrid Journal   (Followers: 201)
Diabetologia Kliniczna     Hybrid Journal  
Diabetologie und Stoffwechsel     Hybrid Journal   (Followers: 2)
Egyptian Journal of Haematology     Open Access  
eJHaem     Open Access  
European Journal of Haematology     Hybrid Journal   (Followers: 16)
Experimental Hematology     Hybrid Journal   (Followers: 6)
Experimental Hematology & Oncology     Open Access   (Followers: 6)
Expert Review of Hematology     Hybrid Journal   (Followers: 5)
Fluids and Barriers of the CNS     Open Access   (Followers: 1)
Global Journal of Transfusion Medicine     Open Access   (Followers: 1)
Haematologica - the Hematology journal     Open Access   (Followers: 33)
Haemophilia     Hybrid Journal   (Followers: 66)
Hematologia     Full-text available via subscription   (Followers: 3)
Hematología     Open Access  
Hematology     Open Access   (Followers: 15)
Hematology Reports     Open Access   (Followers: 4)
Hematology, Transfusion and Cell Therapy     Open Access   (Followers: 2)
Hematology/Oncology and Stem Cell Therapy     Open Access   (Followers: 6)
Hemodialysis International     Hybrid Journal   (Followers: 3)
Hepatitis Monthly     Open Access   (Followers: 3)
Immunohematology : Journal of Blood Group Serology and Molecular Genetics     Hybrid Journal   (Followers: 1)
Indian Journal of Hematology and Blood Transfusion     Hybrid Journal   (Followers: 2)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
InFo Hämatologie + Onkologie : Interdisziplinäre Fortbildung von Ärzten für Ärzte     Full-text available via subscription  
Integrated Blood Pressure Control     Open Access  
International Blood Research & Reviews     Open Access  
International Journal of Clinical Transfusion Medicine     Open Access   (Followers: 3)
International Journal of Diabetes in Developing Countries     Hybrid Journal   (Followers: 6)
International Journal of Diabetes Research     Open Access   (Followers: 8)
International Journal of Hematologic Oncology     Open Access   (Followers: 2)
International Journal of Hematology     Hybrid Journal   (Followers: 4)
International Journal of Hematology Research     Open Access   (Followers: 2)
International Journal of Hematology-Oncology and Stem Cell Research     Open Access   (Followers: 2)
International Journal of Laboratory Hematology     Hybrid Journal   (Followers: 25)
Iraqi Journal of Hematology     Open Access  
JMIR Diabetes     Open Access  
Journal of Blood Disorders & Transfusion     Open Access   (Followers: 3)
Journal of Applied Hematology     Open Access   (Followers: 2)
Journal of Blood Medicine     Open Access   (Followers: 1)
Journal of Cerebral Blood Flow & Metabolism     Hybrid Journal   (Followers: 3)
Journal of Diabetes     Open Access   (Followers: 20)
Journal of Diabetes and its Complications     Hybrid Journal   (Followers: 25)
Journal of Diabetes and Metabolic Disorders     Open Access   (Followers: 8)
Journal of Diabetes Investigation     Open Access   (Followers: 12)
Journal of Diabetes Mellitus     Open Access   (Followers: 5)
Journal of Diabetes Research     Open Access   (Followers: 13)
Journal of Diabetes Research     Open Access   (Followers: 9)
Journal of Hematological Malignancies     Open Access  
Journal of Hematology     Open Access   (Followers: 2)
Journal of Hematology and Transfusion Medicine     Open Access   (Followers: 1)
Journal of Hematopathology     Hybrid Journal   (Followers: 3)
Journal of Hypo & Hyperglycemia     Partially Free  
Journal of Pediatric Hematology/Oncology     Hybrid Journal   (Followers: 8)
Journal of Social Health and Diabetes     Open Access   (Followers: 1)
Journal of Thrombosis and Haemostasis     Hybrid Journal   (Followers: 80)
Journal of Thrombosis and Thrombolysis     Hybrid Journal   (Followers: 35)
Journal of Transfusion Medicine     Full-text available via subscription  
Kidney and Blood Pressure Research     Open Access   (Followers: 4)
Leukemia     Hybrid Journal   (Followers: 22)
Leukemia and Lymphoma     Hybrid Journal   (Followers: 12)
Leukemia Research     Hybrid Journal   (Followers: 8)
Leukemia Research Reports     Open Access   (Followers: 1)
Leukemia Supplements     Full-text available via subscription  
Mediterranean Journal of Hematology and Infectious Diseases     Open Access  
Nederlands Tijdschrift voor Diabetologie     Hybrid Journal  
Nutrition & Diabetes     Open Access   (Followers: 20)
Oncohematology     Open Access   (Followers: 1)
Open Diabetes Journal     Open Access  
Open Hematology Journal     Open Access   (Followers: 1)
Open Hypertension Journal     Open Access  
Open Journal of Blood Diseases     Open Access  
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 8)
Pediatric Hematology Oncology Journal     Open Access   (Followers: 3)
Peritoneal Dialysis International     Hybrid Journal  
Platelets     Hybrid Journal   (Followers: 3)
Practical Diabetes     Hybrid Journal   (Followers: 7)
Primary Care Diabetes     Hybrid Journal   (Followers: 26)
Research & Reviews : Journal of Oncology and Hematology     Full-text available via subscription   (Followers: 1)
Research and Practice in Thrombosis and Haemostasis     Open Access   (Followers: 1)
Revista Cubana de Hematología, Inmunología y Hemoterapia     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Thrombosis and Hemostasis     Hybrid Journal   (Followers: 45)
Thalassemia Reports     Open Access   (Followers: 1)
The Lancet Haematology     Full-text available via subscription   (Followers: 38)
Therapeutic Advances in Hematology     Hybrid Journal  
Thrombosis & Haemostasis     Hybrid Journal   (Followers: 140)
Thrombosis Research     Hybrid Journal   (Followers: 47)
Transfusionsmedizin - Immunhämatologie, Hämotherapie, Immungenetik, Zelltherapie     Hybrid Journal  
Transplantation and Cellular Therapy     Hybrid Journal   (Followers: 13)
Veins and Lymphatics     Open Access   (Followers: 1)


Similar Journals
Journal Cover
Haematologica - the Hematology journal
Journal Prestige (SJR): 3.063
Citation Impact (citeScore): 4
Number of Followers: 33  

  This is an Open Access Journal Open Access journal
ISSN (Print) 0390-6078 - ISSN (Online) 1592-8721
Published by Ferrata Storti Foundation Homepage  [1 journal]
  • Images from the Haematologica Atlas of Hematologic Cytology: congenital
           dyserythropoietic anemia type II

    • Authors: Rosangela Invernizzi
      PubDate: Mon, 01 Aug 2022 00:00:00 +000
  • The polymerase chain reaction, so simple, so clever: the discovery that
           made minimal residual disease come true

    • Authors: Hélène Cavé
      PubDate: Mon, 01 Aug 2022 00:00:00 +000
  • Low-dose tyrosine kinase inhibitors in patients with chronic myeloid
           leukemia: a retrospective study in China

    • Authors: Yilin Chen; Zelin Liu, Jing Zou, Danyu Wang, Wenjuan He, Li Meng, Fanjun Cheng, Yanli Zhang, Weiming Li
      PubDate: Thu, 28 Apr 2022 00:00:00 +000
  • Copy number alterations define outcome in Philadelphia chromosome-positive
           acute lymphoblastic leukemia

    • Authors: Helena Hohtari; Niels Pallisgaard, Matti Kankainen, Pekka Ellonen, Oscar Brück, Timo Siitonen, Marjaana Säily, Marjatta Sinisalo, Marja Pyörälä, Maija Itälä-Remes, Perttu Koskenvesa, Erkki Elonen, Satu Mustjoki, Kimmo Porkka
      PubDate: Thu, 28 Apr 2022 00:00:00 +000
  • PD-1/PD-L1 expression is frequent and correlated with lymphocyte density
           in Erdheim-Chester disease

    • Authors: Frederic Charlotte; Fleur Cohen-Aubart, Levi-Dan Azoulay, Zahir Amoura, Jean-Francois Emile, Julien Haroche
      PubDate: Thu, 28 Apr 2022 00:00:00 +000
  • Blood cell and marrow changes in patients with Kikuchi disease

    • Authors: Shan-Chi Yu; Huai-Hsuan Huang, Chun-Nan Chen, Tseng-Cheng Chen, Tsung-Lin Yang
      PubDate: Thu, 28 Apr 2022 00:00:00 +000
  • Hemostatic and protein C pathway dysfunction in the pathogenesis of
           experimental cerebral malaria

    • Authors: Niamh O'Regan; Kristina Gegenbauer, Eimear M. Gleeson, Kenji Fukudome, Jamie M. O'Sullivan, Clive Drakeford, Niall Dalton, Alain Chion, Teresa M. Brophy, Owen P. Smith, Roger J.S. Preston, James S. O'Donnell
      PubDate: Thu, 21 Apr 2022 00:00:00 +000
  • COVID-19 infection in acute lymphoblastic leukemia over 15 months of the
           pandemic. A Campus ALL report

    • Authors: Sabina Chiaretti; Massimiliano Bonifacio, Roberta Agrippino, Fabio Giglio, Mario Annunziata, Antonio Curti, Maria Ilaria Del Principe, Prassede Salutari, Mariarita Sciumè, Mario Delia, Marco Armenio, Valentina Mancini, Antonino Mulè, Francesco Grimaldi, Giovanna Rege-Cambrin, Lidia Santoro, Federico Lussana, Patrizia Chiusolo, Crescenza Pasciolla, Anna Maria Scattolin, Marco Cerrano, Maria Ciccone, Marzia Defina, Fabio Forghieri, Carla Mazzone, Matteo Piccini, Felicetto Ferrara, Giovanni Pizzolo, Robin Foà
      PubDate: Thu, 21 Apr 2022 00:00:00 +000
  • A novel BCMA CAR-T-cell therapy with optimized human scFv for treatment of
           relapsed/refractory multiple myeloma: results from phase I clinical trials

    • Authors: Min Yang; Wenhao Zhang, Kang Yu, Peng Wang, Hua Jiang, Linjun Chen, Haitao Meng, Yiqin Weng, Rong Tao, Xin Huang, Chongyun Xing, Huamao Wang, Jiangbo Wan, Shasha Wang, Lihui Dai, Amanda Y. Hendrix, Jun Xiao, Wei Wang, Hong Ma, Siguo Hao, Jie Jin, Zonghai Li, Songfu Jiang
      PubDate: Thu, 21 Apr 2022 00:00:00 +000
  • Treatment of leptomeningeal disease in blastic plasmacytoid dendritic cell
           neoplasm following tagraxofusp-erzs induction

    • Authors: Deepak B. Vangala; Verena Nilius-Eliliwi, Thomas Mika, Thilo Gambichler, Rene Stranzenbach, Roland Schroers
      PubDate: Thu, 07 Apr 2022 00:00:00 +000
  • Full versus prophylactic-intermediate doses of anticoagulants in
           COVID-19: a meta-analysis

    • Authors: Lorenzo Loffredo; Augusto Di Castelnuovo, Giovanni Alfonso Chiariello, Pasquale Pignatelli, Francesco Violi
      PubDate: Thu, 31 Mar 2022 00:00:00 +000
  • The use of hydroxyurea pretreatment in chronic myeloid leukemia in the
           current tyrosine kinase inhibitor era

    • Authors: Camille C.B. Kockerols; Inge Geelen, Mark-David Levin, Jeroen J.W.M. Janssen, Avinash G. Dinmohamed, Mels Hoogendoorn, Jan J. Cornelissen, Peter E. Westerweel
      PubDate: Thu, 31 Mar 2022 00:00:00 +000
  • Preclinical evaluation of the preservation of red blood cell concentrates
           by hypoxic storage technology for transfusion in sickle cell disease

    • Authors: Laura Bencheikh; Kim-Anh Nguyen, Philippe Chadebech, Laurent Kiger, Gwellaouen Bodivit, Alicia Jouard, Sadaf Pakdaman, Sandia Adypagavane, Etienne Audureau, Khouloud Tebbakha, Thibaut Bocquet, Blandine Mignen, Nicolas Hebert, Marion Seguin, France Pirenne, Samuel Sowemimo-Coker, Andrew Dunham, Pablo Bartolucci
      PubDate: Thu, 31 Mar 2022 00:00:00 +000
  • Distinct genetic alterations in Burkitt-like lymphoma with 11q aberration
           and Burkitt lymphoma: a novel case report of composite lymphoma

    • Authors: Meejeong Kim; Hee Sang Hwang, Dok Hyun Yoon, Sung-Min Chun, Heounjeong Go
      PubDate: Thu, 31 Mar 2022 00:00:00 +000
  • Cell-free DNA sequencing as a potential screening tool for phase I
           targeted treatment in refractory/relapse diffuse large B-cell lymphoma

    • Authors: Cyril Quivoron; Anthony Tarabay, Jean-Marie Michot, Arnaud Pagès, Hélène Lecourt, Anne Aupérin, Alina Danu, Julien Lazarovici, Julien Rossignol, David Ghez, Peggy Dartigues, Véronique Vergé, Christophe Massard, Valérie Camara-Clayette, Vincent Ribrag, Clémentine Sarkozy
      PubDate: Thu, 24 Mar 2022 00:00:00 +000
  • Alloimmunization against Fy3 is a serious threat in the era of cell

    • Authors: Baptiste Lemaire; Sophie Waldvogel Abramowski
      PubDate: Thu, 03 Mar 2022 00:00:00 +000
  • Intricacies of GATA-ca, continued

    • Authors: Christine Lomas-Francis; Elizabeth F. Stone, Connie M. Westhoff, Patricia A. Shi
      PubDate: Thu, 03 Mar 2022 00:00:00 +000
  • Functional testing of relapsed chronic lymphocytic leukemia guides
           precision medicine and maps response and resistance mechanisms. An index

    • Authors: Sigrid S. Skånland; Marit Inngjerdingen, Henrik Bendiksen, Jamie York, Signe Spetalen, Ludvig A. Munthe, Geir E. Tjønnfjord
      PubDate: Thu, 03 Mar 2022 00:00:00 +000
  • A novel CD34-specific T-cell engager efficiently depletes acute myeloid
           leukemia and leukemic stem cells in vitro and in vivo

    • Authors: Lucas C. M. Arruda; Arwen Stikvoort, Melanie Lambert, Liqing Jin, Laura Sanchez Rivera, Renato M. P. Alves, Tales Rocha de Moura, Carsten Mim, Sören Lehmann, Rebecca Axelsson-Robertson, John E. Dick, Jonas Mattsson, Björn Önfelt, Mattias Carlsten, Michael Uhlin
      Abstract: Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34+ blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34+CD38- phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34+ hematopoietic stem cells from peripheral blood stem cell grafts and CD34+ blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34+ blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
      PubDate: Thu, 10 Feb 2022 00:00:00 +000
  • Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor
           secretion by controlling Golgi architecture

    • Authors: Marije Kat; Ellie Karampini, Arie J. Hoogendijk, Petra E. Bürgisser, Aat A. Mulder, Floris P.J. van Alphen, Jenny Olins, Dirk Geerts, Maartje van den Biggelaar, Coert Margadant, Jan Voorberg, Ruben Bierings
      Abstract: Von Willebrand factor (VWF) is a multimeric hemostatic protein primarily synthesized in endothelial cells. VWF is stored in endothelial storage organelles, the Weibel-Palade bodies (WPB), whose biogenesis strongly depends on VWF anterograde trafficking and Golgi architecture. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. We previously identified the SNARE SEC22B, which is involved in anterograde endoplasmic reticulum-to-Golgi transport, as a novel regulator of WPB elongation. To elucidate novel determinants of WPB morphology we explored endothelial SEC22B interaction partners in a mass spectrometry-based approach, identifying the Golgi SNARE Syntaxin 5 (STX5). We established STX5 knockdown in endothelial cells using shRNA-dependent silencing and analyzed WPB and Golgi morphology, using confocal and electron microscopy. STX5-depleted endothelial cells exhibited extensive Golgi fragmentation and decreased WPB length, which was associated with reduced intracellular VWF levels, and impaired stimulated VWF secretion. However, the secretion-incompetent organelles in shSTX5 cells maintained WPB markers such as Angiopoietin 2, P-selectin, Rab27A, and CD63. In brief, we identified SNARE protein STX5 as a novel regulator of WPB biogenesis.
      PubDate: Thu, 27 Jan 2022 00:00:00 +000
  • Programmed cell death ligand 1 expression in aggressive pediatric
           non-Hodgkin lymphomas: frequency, genetic mechanisms, and clinical

    • Authors: Kevin E. Fisher; Lizmery S. Ferguson, Amy M. Coffey, Brian Y. Merritt, Jonathan L. Curry, Andrea N. Marcogliese, Angela M. Major, Kala Y. Kamdar, Dolores H. Lopez-Terrada, Choladda V. Curry
      Abstract: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are immunomodulatory molecules overexpressed in lymphomas and are promising immunotherapy targets for hematologic malignancies. However, studies of PD-1/PD-L1 overexpression and their clinical significance in aggressive pediatric non-Hodgkin lymphomas (NHL) are limited. We assessed PD-1/PD-L1 overexpression using immunohistochemistry in 68 aggressive pediatric NHL: ALK-positive anaplastic large cell lymphoma (ALK+ ALCL, n=8), Burkitt lymphoma (BL, n=27), and large B-cell lymphoma (LBCL) de novo LBCL, n=22 and diffuse LBCL arising as monomorphic post-transplant lymphoproliferative disorder [PTLD-DLBCL], n=11. In LBCL, correlations between PD-L1 overexpression and Epstein-Barr virus (EBV) status, cell of origin, stage, nodal status, overall survival (OS), and event-free survival (EFS) were examined. The genetic mechanisms of PD-L1 overexpression were investigated using targeted next-generation sequencing (NGS) and cytogenetic data. All ALK+ ALCL samples, 50.0% of de novo LBCL (11/22), 72.7% of PTLD-DLBCL (8/11), and no BL overexpressed PD-L1. Overexpressed PD-L1 correlated with EBV positivity (P=0.033) in LBCL and lower EFS in de novo LBCL (P=0.017). NGS of select LBCL revealed distinct somatic mutations and an ultra-hypermutated PTLD-DLBCL. Most cases with 9p24.1 copy gains overexpressed PD-L1 although some cases had no discernible genetic drivers of PD-L1 overexpression. Overexpressed PD-L1 is common in pediatric LBCL, associated with EBV positivity and 9p24.1 gains, and may have prognostic significance in de novo LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in aggressive pediatric NHL can occur. Thus, additional studies exploring the therapeutic and prognostic significance and molecular mechanisms of PD-L1 overexpression in aggressive pediatric NHL are warranted.
      PubDate: Thu, 27 Jan 2022 00:00:00 +000
  • Occurrence of a paroxysmal nocturnal hemoglobinuria clone in an essential
           thrombocythemia: a link between PIGV and MPL

    • Authors: Alexej Knaus; François Vergez, Cédric Garcia, Hartmut Engels, Hela Hundertmark, David Ribes, Laetitia Largeaud, Suzanne Tavitian, Bernard Payrastre, Peter Krawitz, Stanislas Faguer, Agnes Ribes
      PubDate: Thu, 27 Jan 2022 00:00:00 +000
  • Comprehensive genomic analysis of refractory multiple myeloma reveals a
           complex mutational landscape associated with drug resistance and novel
           therapeutic vulnerabilities

    • Authors: Nicola Giesen; Nagarajan Paramasivam, Umut H. Toprak, Daniel Huebschmann, Jing Xu, Sebastian Uhrig, Mehmet Samur, Stella Bähr, Martina Fröhlich, Sadaf S. Mughal, Elias K. Mai, Anna Jauch, Carsten Müller-Tidow, Benedikt Brors, Nikhil Munshi, Hartmut Goldschmidt, Niels Weinhold, Matthias Schlesner, Marc S. Raab
      Abstract: The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. In this study, we performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity; the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients; a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.
      PubDate: Thu, 20 Jan 2022 00:00:00 +000
  • B-cell antigen receptor expression and phosphatidylinositol 3-kinase
           signaling regulate genesis and maintenance of mouse chronic lymphocytic

    • Authors: Vera Kristin Schmid; Ahmad Khadour, Nabil Ahmed, Carolin Brandl, Lars Nitschke, Klaus Rajewsky, Hassan Jumaa, Elias Hobeika
      Abstract: Chronic lymphocytic leukemia (CLL) is a frequent lymphoproliferative disorder of B cells. Although inhibitors targeting signal proteins involved in B-cell antigen receptor (BCR) signaling constitute an important part of the current therapeutic protocols for CLL patients, the exact role of BCR signaling, as compared to genetic aberration, in the development and progression of CLL is controversial. In order to investigate whether BCR expression per se is pivotal for the development and maintenance of CLL B cells, we used the TCL1 mouse model. By ablating the BCR in CLL cells from TCL1 transgenic mice, we show that CLL cells cannot survive without BCR signaling and are lost within 8 weeks in diseased mice. Furthermore, we tested whether mutations augmenting B-cell signaling influence the course of CLL development and its severity. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity is indispensable for B-cell survival. It is negatively regulated by the lipid phosphatase PTEN, whose loss mimics PI3K pathway activation. Herein, we show that PTEN has a key regulatory function in the development of CLL, as deletion of the Pten gene resulted in greatly accelerated onset of the disease. By contrast, deletion of the gene TP53, which encodes the tumor suppressor p53 and is highly mutated in CLL, did not accelerate disease development, confirming that development of CLL was specifically triggered by augmented PI3K activity through loss of PTEN and suggesting that CLL driver consequences most likely affect BCR signaling. Moreover, we could show that in human CLL patient samples, 64% and 81% of CLL patients with a mutated and unmutated IgH VH, respectively, show downregulated PTEN protein expression in CLL B cells if compared to healthy donor B cells. Importantly, we found that B cells derived from CLL patients had higher expression levels of the miRNA-21 and miRNA-29, which suppresses PTEN translation, compared to healthy donors. The high levels of miRNA-29 might be induced by increased PAX5 expression of the B-CLL cells. We hypothesize that downregulation of PTEN by increased expression levels of miR-21, PAX5 and miR-29 could be a novel mechanism of CLL tumorigenesis that is not established yet. Together, our study demonstrates the pivotal role for BCR signaling in CLL development and deepens our understanding of the molecular mechanisms underlying the genesis of CLL and for the development of new treatment strategies.
      PubDate: Thu, 13 Jan 2022 00:00:00 +000
  • Immune pathway upregulation and lower genomic instability distinguish
           EBV-positive nodal T/NK-cell lymphoma from ENKTL and PTCL-NOS

    • Authors: Cho Mar Myint Wai; Shangying Chen, The Phyu, Shuangyi Fan, Sai Mun Leong, Wenning Zheng, Louis Ching Yi Low, Shoa-Nian Choo, Chi-Kuen Lee, Tae-Hoon Chung, Kenneth Hon Kim Ban, Soumita Ghosh, Stefanus Lie, Seiichi Kato, Shigeo Nakamura, Emiko Takahashi, Young-Hyeh Ko, Joseph D. Khoury, Shih-Sung Chuang, Rex K.H. Au-Yeung, Soo-Yong Tan, Soon-Thye Lim, Choon-Kiat Ong, Yong-Howe Ho, Li Mei Poon, Sanjay de Mel, Anand D. Jeyasekharan, Wee-Joo Chng, Franziska Otto, Leticia Quintanilla-Martinez, Federica Zanardi, Fabio Iannelli, Claudio Tripodo, Jason J. Pitt, Siok-Bian Ng
      Abstract: Primary Epstein-Barr virus (EBV)-positive nodal T/NK-cell lymphoma (PTCL-EBV) is a poorly understood disease which shows features resembling extranodal NK/T-cell lymphoma (ENKTL) and is currently not recognized as a distinct entity but categorized as a variant of primary T-cell lymphoma not otherwise specified (PTCL-NOS). Herein, we analyzed copynumber aberrations (n=77) with a focus on global measures of genomic instability and homologous recombination deficiency and performed gene expression (n=84) and EBV miRNA expression (n=24) profiling as well as targeted mutational analysis (n=16) to further characterize PTCL-EBV in relation to ENKTL and PTCL-NOS. Multivariate analysis revealed that patients with PTCL-EBV had a significantly worse outcome compared to patients with PTCL-NOS (P=0.002) but not to those with ENKTL. Remarkably, PTCL-EBV exhibited significantly lower genomic instability and homologous recombination deficiency scores compared to ENKTL and PTCL-NOS. Gene set enrichment analysis revealed that many immune-related pathways, interferon α/γ response, and IL6_JAK_STAT3 signaling were significantly upregulated in PTCLEBV and correlated with lower genomic instability scores. We also identified that NFκB-associated genes, BIRC3, NFKB1 (P50) and CD27, and their proteins are upregulated in PTCL-EBV. Most PTCL-EBV demonstrated a type 2 EBV latency pattern and, strikingly, exhibited downregulated expression of most EBV miRNA compared to ENKTL and their target genes were also enriched in immune-related pathways. PTCL-EBV also showed frequent mutations of TET2, PIK3CD and STAT3, and are characterized by microsatellite stability. Overall, poor outcome, low genomic instability, upregulation of immune pathways and downregulation of EBV miRNA are distinctive features of PTCL-EBV. Our data support the concept that PTCL-EBV could be considered as a distinct entity, provide novel insights into the pathogenesis of the disease and offer potential new therapeutic targets for this tumor.
      PubDate: Thu, 13 Jan 2022 00:00:00 +000
  • Sorting nexin 24 is required for α-granule biogenesis and cargo
           delivery in megakaryocytes

    • Authors: Joanne Lacey; Simon J. Webster, Paul R. Heath, Chris J. Hill, Lucinda Nicholson-Goult, Bart E. Wagner, Abdullah O. Khan, Neil V. Morgan, Michael Makris, Martina E. Daly
      Abstract: Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harboring a DNA-binding variant of FLI1. Our analysis identified 2,276 transcripts that were differentially expressed in FLI1-deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an induced pluripotent stem cell-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (P=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localization studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.
      PubDate: Thu, 13 Jan 2022 00:00:00 +000
  • Effects of corticosteroids in patients with sickle cell disease and acute
           complications: a systematic review and meta-analysis

    • Authors: Julien Lopinto; Segolene Gendreau, Enora Berti, Pablo Bartolucci, Anoosha Habibi, Armand Mekontso Dessap
      Abstract: Whether corticosteroids improve outcome in patients with acute complications of sickle cell disease (SCD) is still debated. We performed a systematic review of the literature with the aim of estimating effects of corticosteroids on the clinical course of vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) in patients with SCD. The primary outcome was transfusion requirement during hospitalization. Studies were identified by search of MEDLINE and CENTRAL database. Three randomized clinical trials (RCT) and three retrospective cohort studies (RCS) were included, involving 3,304 participants and 5,562 VOC or ACS episodes. There was no difference between corticosteroids and standard treatment regarding transfusion requirement overall (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.38-2.53) but there was a significant interaction of the study type (P<0.0001): corticosteroid therapy was associated with a lower risk of transfusion in RCT (OR=0.13, 95% CI: 0.04-0.45) and a higher risk of transfusion in RCS (OR=2.12, 95% CI: 1.33-3.40. In RCT, the length of hospital stay was lower with corticosteroids as compared with standard treatment: mean difference - 24 hours (95% CI: -35 to -14). Corticosteroids were associated with an increased risk of hospital readmission as compared with standard treatment, in RCT, RCS, and the entire cohort: OR=5.91, 95% CI: 1.40-24.83; OR=3.28, 95% CI: 1.46-7.36 and OR=3.21, 95% CI: 1.97-5.24, respectively. Corticosteroids were associated with reduced number of transfusions and length of stay in RCT but not in RCS, with more rehospitalizations overall. Additional RCT should be conducted while minimizing the risk of rehospitalizations.
      PubDate: Thu, 13 Jan 2022 00:00:00 +000
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Heriot-Watt University
Edinburgh, EH14 4AS, UK
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