Membrane protein CAR promotes hematopoietic regeneration upon stress.
Abstract Adult hematopoietic stem cells (HSCs) are quiescent most of the time, and how HSCs switch from quiescence to proliferation following hematopoietic stress is unclear. Here we demonstrate that upon stress the coxsackievirus and adenovirus receptor CAR (also known as CXADR) is upregulated in HSCs and critical for HSC entry into the cell cycle. WT HSCs were detected more rapid repopulation ability than the CAR cKO counterparts. After 5-FU treatment, CAR cKO HSCs had lower levels of Notch1 expression and elevated protein level of Numb, a Notch antagonist. The Notch signaling inhibitor DAPT, dominant negative f...
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Wu G, Zhang CC Tags: Haematologica Source Type: research

Chronic lymphocytic leukaemia and prolymphocytic leukaemia. Two coins or two sides of the same coin?
, Villamor N, Matutes E PMID: 32586902 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Magnano L, Navarro A, López-Guerra M, Clot G, Beà S, Bastidas G, Costa D, Rivero A, Garrote M, Giné E, Rozman M, Aymerich M, Colomer D, López-Guillermo A, Campo E, Villamor N, Matutes E Tags: Haematologica Source Type: research

Reveromycin A, a novel acid-seeking agent, ameliorates bone destruction and tumor growth in multiple myeloma.
PMID: 32586903 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Watanabe K, Bat-Erdene A, Tenshin H, Cui Q, Teramachi J, Hiasa M, Oda A, Harada T, Miki H, Sogabe K, Oura M, Sumitani R, Mitsui Y, Endo I, Tanaka E, Kawatani M, Osada H, Matsumoto T, Abe M Tags: Haematologica Source Type: research

In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor.
We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364. This molecule potently inhibits the methyltransferase activity of DNMT1, but not DNMT family members DNMT3A or DNMT3B. In contrast with cytidine analog DNMT inhibitors, the DNMT1 inhibitory mechanism of GSK3482364 does not require DNA incorporation and is reversible. In cultured human erythroid progenitor cells (EPCs), GSK3482364 decreased overall DNA methylation resulting in de-repression of the gamma globin genes HBG1 and HBG2 and increased HbF expression. In a transgenic mouse model of sickle cel...
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Gilmartin AG, Groy A, Gore ER, Atkins C, Long ER, Montoute MN, Wu Z, Halsey W, McNulty DE, Ennulat D, Rueda L, Pappalardi M, Kruger RG, McCabe MT, Raoof A, Butlin R, Stowell A, Cockerill M, Waddell I, Ogilvie D, Luengo J, Jordan A, Benowitz AB Tags: Haematologica Source Type: research

Infrequent "chronic lymphocytic leukemia-specific" immunoglobulin stereotypes in aged individuals with or without low count monoclonal B cell lymphocytosis.
Infrequent "chronic lymphocytic leukemia-specific" immunoglobulin stereotypes in aged individuals with or without low count monoclonal B cell lymphocytosis. Haematologica. 2020 Jun 25;: Authors: Agathangelidis A, Galigalidou C, Scarfò L, Moysiadis T, Rovida A, Gounari M, Psomopoulos F, Ranghetti P, Galanis A, Davi F, Stamatopoulos K, Chatzidimitriou A, Ghia P PMID: 32586905 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Agathangelidis A, Galigalidou C, Scarfò L, Moysiadis T, Rovida A, Gounari M, Psomopoulos F, Ranghetti P, Galanis A, Davi F, Stamatopoulos K, Chatzidimitriou A, Ghia P Tags: Haematologica Source Type: research

miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis.
, Menéndez R, Andrés V, González-Conejero R, Martínez C Abstract Neutrophil extracellular traps (NETs) induce a procoagulant response linking inflammation and thrombosis. Low levels of miR-146a, a brake of inflammatory response, are involved in higher risk for cardiovascular events, but the mechanisms explaining how miR-146a exerts its function remain largely undefined. The aim of this study was to explore the impact of miR-146a deficiency in NETosis both, in sterile and non-sterile models in vivo, and to inquire into the underlying mechanism. Two models of inflammation were performed: ...
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Arroyo AB, Fernández-Pérez MP, Del Monte A, Águila S, Méndez R, Hernández-Antolín R, García-Barber N, de Los Reyes-García AM, González-Jiménez P, Arcas MI, Vicente V, Menéndez R, Andrés V, González-Conejero R, Martínez C Tags: Haematologica Source Type: research

Anemia and hemodilution: analysis of a single center cohort based on 2858 Red Cell Mass measurements.
PMID: 32586907 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Drevon L, Maslah N, Soret-Dulphy J, Dosquet C, Ravdan O, Vercellino L, Belkhodja C, Parquet N, Brignier AC, Schlageter MH, Cassinat B, Kiladjian JJ, Chomienne C, Giraudier S, FIM, French Intergroup for Myeloproliferative disorders Tags: Haematologica Source Type: research

Isatuximab plus pomalidomide and dexamethasone in elderly patients with relapsed/refractory multiple myeloma: ICARIA-MM subgroup analysis.
PMID: 32586908 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 25, 2020 Category: Hematology Authors: Schjesvold FH, Richardson PG, Facon T, Alegre A, Spencer A, Jurczyszyn A, Sunami K, Frenzel L, Min CK, Guillonneau S, Lin PL, Le-Guennec S, Campana F, van de Velde H, Bensfia S, Bringhen S Tags: Haematologica Source Type: research

Germline pathogenic variants in transcription factors predisposing to pediatric acute myeloid leukemia: results from the French ELAM02 trial.
PMID: 32554555 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Fenwarth L, Duployez N, Marceau-Renaut A, Abou Chahla W, Ducassou S, Gandemer V, Pasquet M, Leblanc T, Schneider P, Domenech C, Saultier P, Leverger G, Lapillonne H, Preudhomme C, Petit A Tags: Haematologica Source Type: research

Concomitant constitutive LNK and NFE2 mutation with loss of sumoylation in a case of hereditary thrombocythemia.
Pahl HL PMID: 32554556 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Böckelmann LC, Basu T, Gründer A, Wang W, Breucker J, Kaiser S, Pichler A, Pahl HL Tags: Haematologica Source Type: research

Human platelets are a source of collagen I.
PMID: 32554557 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Kyselova A, Zukunft S, Puppe D, Wittig I, Mann WA, Dornauf I, Fleming I, Randriamboavonjy V Tags: Haematologica Source Type: research

Clonal haematopoietic mutations linked to platelet traits and the risk of thrombosis or bleeding.
Abstract Platelets are key elements in thrombosis, particularly in atherosclerosis-associated arterial thrombosis (atherothrombosis), and haemostasis. Megakaryocytes in the bone marrow, differentiated from haematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, including essential thrombocytosis, indicate that not only inherited but also somatic mutations in haematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-haemorrhagic complications regula...
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Veninga A, de Simone I, Heemskerk JWM, Ten Cate H, van der Meijden PEJ Tags: Haematologica Source Type: research

The acquired von Willebrand syndrome focused for hematologists.
Abstract The acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike the inherited disease, the AVWS occurs in persons with no personal or family history of bleeding and is often associated with a variety of underlying diseases, most frequently lymphoproliferative, myeloproliferative and cardiovascular disorders. After the presentation of a typical case, in this narrative review we discuss the more recent data on the pathophysiology, clinical, laboratory and therapeutic aspects of this acquired bleeding syndr...
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Franchini M, Mannucci PM Tags: Haematologica Source Type: research

Impact on survival through consolidation radiotherapy for diffuse large B-cell lymphoma: a comprehensive meta-analysis.
k U Abstract Rituximab has improved response rates and overall survival in B-cell lymphoma (DLBCL). Radiotherapy is an effective treatment modality for lymphomas, but there is uncertainty on its use as consolidation after chemo-immunotherapy mainly in advanced stages. We evaluated its efficacy with a comprehensive meta-analysis and a systematic search of Pubmed, Embase, Cochrane, and abstracts from ASCO, ASH, ESMO and ASTRO published from June 1966 and December 2018. We identified 11 trials that evaluated consolidation radiotherapy following chemotherapy in a randomized fashion in 4'584 patients. The primary endpo...
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Berger MD, Trelle S, Büchi AE, Jegerlehner S, Ionescu C, Lamy de la Chapelle T, Novak U Tags: Haematologica Source Type: research

Transfer of stem cell niche-residential regulatory T cells prevents post-irradiation bone marrow injury.
PMID: 32554561 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Kakiuchi M, Hirata Y, Robson SC, Fujisaki J Tags: Haematologica Source Type: research

Comparison of total body irradiation versus non- total body irradiation containing regimens for de novo acute myeloid leukemia in children.
Abstract With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, p
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Dandoy CE, Davies SM, Ahn KW, He Y, Kolb AE, Levine J, Bo-Subait S, Abdel-Azim H, Bhatt N, Chewing J, Gadalla S, Gloude N, Hayashi R, Lalefar NR, Law J, MacMillan M, O'Brien T, Prestidge T, Sharma A, Shaw P, Winestone L, Eapen M Tags: Haematologica Source Type: research

Targeting GLUT1 in acute myeloid leukemia to overcome cytarabine resistance.
ersson K PMID: 32554563 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Åbacka H, Hansen JS, Huang P, Venskutonytė R, Hyrenius-Wittsten A, Poli G, Tuccinardi T, Granchi C, Minutolo F, Hagström-Andersson AK, Lindkvist-Petersson K Tags: Haematologica Source Type: research

Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicentric trial.
abrespine A, Bay JO, Leblond V, Dhédin N, French Innovative Leukemia Organization (FILO), Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine taper...
Source: Haematologica - June 11, 2020 Category: Hematology Authors: Tournilhac O, Le Garff-Tavernier M, Nguyen Quoc S, Forcade E, Chevallier P, Legrand-Izadifar F, Damaj GL, Michonneau D, Tomowiak C, Borel C, Orvain C, Turlure P, Redjou R, Guillerm G, Vincent L, Simand C, Lemal R, Quiney C, Combes P, Pereira B, Calvet L, Tags: Haematologica Source Type: research

Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay.
Abstract The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Here, through a detailed examination of hemopoiesis from murine GATA1s ES cells and GATA1s e...
Source: Haematologica - June 11, 2020 Category: Hematology Authors: Juban G, Sakakini N, Chagraoui H, Cruz Hernandez D, Cheng Q, Soady K, Stoilova B, Garnett C, Waithe D, Otto G, Doondeea J, Usukhbayar B, Karkoulia E, Alexiou M, Strouboulis J, Morrissey E, Roberts I, Porcher C, Vyas P Tags: Haematologica Source Type: research

Inherited thrombocytopenias: history, advances and perspectives.
Abstract Within the last 100 years the role of platelets in hemostatic events and their production by megakaryocytes (MKs) has been gradually defined. Progressively, thrombocytopenia was recognized as a cause of bleeding, first through an acquired immune disorder; then from 1948 when the Bernard-Soulier syndrome was first described, inherited thrombocytopenia has become a fascinating source of Mendelian disease. Often the platelet count is severely decreased and platelet size variable; associated platelet function defects often aggravate bleeding. Macrothrombocytopenia (MTP) with enlarged platelets in variable pro...
Source: Haematologica - June 11, 2020 Category: Hematology Authors: Nurden AT, Nurden P Tags: Haematologica Source Type: research

Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential.
Abstract Thrombopoietin (THPO) has long been known to influence megakaryopoiesis and hematopoietic stem and progenitor cells (HSPCs), though the exact mechanisms through which it acts are unknown. Here we show that MPL expression correlates with megakaryopoietic potential of HSPCs and identify a population of quiescent progenitor cells that show limited dependence on THPO signalling. We show that THPO is primarily responsible for maintenance of hematopoietic cells with megakaryocytic (Mk) differentiation potential and their subsequent Mk differentiation and maturation. The loss of Mks in THPO knockout (KO) mouse m...
Source: Haematologica - June 11, 2020 Category: Hematology Authors: O'Neill A, Chin D, Tan D, Abdul Majeed AQBB, Nakamura-Ishizu A, Suda T Tags: Haematologica Source Type: research

COVID-19 in patients with sickle cell disease - a case series from a UK Tertiary Hospital.
PMID: 32527955 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 11, 2020 Category: Hematology Authors: Chakravorty S, Padmore-Payne G, Ike F, Tshibangu V, Graham C, Rees D, Stuart-Smith S Tags: Haematologica Source Type: research

Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens.
GC, Jabbour EJ, Masarova L, Thompson PA, Wang S, Konoplev S, Pierce SA, Ning J, Qiao W, Welch JS, Kantarjian HM, DiNardo CD, Konopleva MY PMID: 32499238 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Maiti A, Rausch CR, Cortes JE, Pemmaraju N, Daver NG, Ravandi F, Garcia-Manero G, Borthakur G, Naqvi K, Ohanian M, Short NJ, Alvarado Y, Kadia TM, Takahashi K, Yilmaz M, Jain N, Kornblau S, Montalban Bravo G, Sasaki K, Andreeff M, Bose P, Ferrajoli A, Iss Tags: Haematologica Source Type: research

A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies.
This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Al-Samkari H, Parnes AD, Goodarzi K, Weitzman JI, Connors JM, Kuter DJ Tags: Haematologica Source Type: research

Clinical acceleration of JAK2 p.V617F driven myeloproliferative disease due to an uncommon homozygous MPL p.Y591D mutation.
PMID: 32499240 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Ong J, Lin JI, Mitchell H, Morgan S, Perkins AC Tags: Haematologica Source Type: research

Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades.
J, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg HJ, Scott BL, McDonald GB, Storb R, Sandmaier BM Abstract We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past twenty years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose t...
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Petersen SL, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hübel K, Hogan WJ, Tags: Haematologica Source Type: research

Epigenetic and functional changes imposed by NUP98-HOXA9 in a genetically engineered model of chronic myeloid leukemia progression.
PMID: 32499242 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Sloma I, Beer P, Desterke C, Bulaeva E, Bilenky M, Carles A, Moksa M, Raghuram K, Brimacombe C, Lambie K, Turhan AG, Wagner-Ballon O, Gaulard P, Humphries K, Hirst M, Eaves CJ Tags: Haematologica Source Type: research

Fc-engineering significantly improves the recruitment of immune effector cells by anti-ICAM-1 antibody MSH-TP15 for myeloma therapy.
p M Abstract Despite several therapeutic advances, patients with multiple myeloma (MM) require additional treatment options since no curative therapy exists yet. In search of a novel therapeutic antibody, we previously applied phage display with myeloma cell screening and developed TP15, a scFv targeting intercellular adhesion molecule 1 (ICAM-1/CD54). To more precisely evaluate the antibody's modes of action, fully human IgG1 antibody variants were generated bearing wild-type (MSH-TP15) or mutated Fc to either enhance (MSH-TP15 Fc-eng.) or prevent (MSH-TP15 Fc k.o.) Fc gamma receptor binding. Especially MSH-TP15 ...
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Klausz K, Cieker M, Kellner C, Rösner T, Otte A, Krohn S, Lux A, Nimmerjahn F, Valerius T, Gramatzki M, Peipp M Tags: Haematologica Source Type: research

Lenalidomide before and after ASCT for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial.
K NCRI Haematological Oncology Clinical Studies Group Abstract The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) was administered before ASCT to patient...
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Allotey D, Shafeek S, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Tags: Haematologica Source Type: research

Frequency and prognostic impact of ZEB2 H1038 and 1072 mutations in childhood B-other acute lymphoblastic leukemia.
Abstract _. PMID: 32499245 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - June 4, 2020 Category: Hematology Authors: Zaliova M, Potuckova E, Lukes J, Winkowska L, Starkova J, Janotova I, Sramkova L, Stary J, Zuna J, Stanulla M, Zimmermann M, Bornhauser B, Bourquin JP, Eckert C, Cario G, Trka J Tags: Haematologica Source Type: research

100-year-old haematologica images: the quarrel about the origin of platelets (ii).
100-YEAR-OLD HAEMATOLOGICA IMAGES: THE QUARREL ABOUT THE ORIGIN OF PLATELETS (II). Haematologica. 2020 Jun;105(6):1467 Authors: Balduini CL PMID: 32482749 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Balduini CL Tags: Haematologica Source Type: research

Keys to drug sensitivity from updated functional work flows.
PMID: 32482750 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Kurtz SE, Tyner JW Tags: Haematologica Source Type: research

To target the untargetable: elucidation of synergy of APR-246 and azacitidine in TP53 mutant myelodysplastic syndromes and acute myeloid leukemia.
PMID: 32482751 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Sallman DA Tags: Haematologica Source Type: research

Peripheral T-cell lymphoma diagnosis: building a molecular tool.
PMID: 32482752 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Piris MA Tags: Haematologica Source Type: research

PIKing the next therapeutic target in multiple myeloma.
PMID: 32482753 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Caro JL, Davies FE Tags: Haematologica Source Type: research

The increasing complexity of the management of core-binding factor acute myeloid leukemia.
PMID: 32482754 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Litzow MR Tags: Haematologica Source Type: research

The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy.
The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020 Jun;105(6):1494-1506 Authors: Pavlasova G, Mraz M Abstract The introduction of anti-CD20 monoclonal antibodies such as rituximab, ofatumumab, or obinutuzumab improved the therapy of B-cell malignancies even though the precise physiological role and regulation of CD20 remains unclear. Furthermore, CD20 expression is highly variable between different B-cell malignancies, patients with the same malignancy, and even between intraclonal subpopulations in an individual patient. Several epig...
Source: Haematologica - June 1, 2020 Category: Hematology Authors: Pavlasova G, Mraz M Tags: Haematologica Source Type: research

Deciphering the Ets-1/2-mediated transcriptional regulation of F8 gene identifies a minimal F8 promoter for hemophilia A gene therapy.
Follenzi A Abstract A major challenge in the development of a gene therapy for hemophilia A (HA) is the selection of cell type- or tissue-specific promoters to ensure factor VIII (FVIII) expression without eliciting an immune response. As liver sinusoidal endothelial cells (LSECs) are the major FVIII source, understanding the transcriptional F8 regulation in these cells would help optimize the minimal F8 promoter (pF8) to efficiently drive FVIII expression. In silico analyses predicted several binding sites (BS) for the E26 transformation-specific (Ets) transcription factors Ets-1 and Ets-2 in the pF8. Reporter a...
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Famà R, Borroni E, Merlin S, Airoldi C, Pignani S, Cucci A, Corà D, Bruscaggin V, Scardellato S, Faletti S, Pelicci G, Pinotti M, Walker GE, Follenzi A Tags: Haematologica Source Type: research

Kreuth V initiative: European consensus proposals for treatment of haemophilia using standard products, extended half-life coagulation factor concentrates and non-replacement therapies.
This report contains the updated consensus recommendations for optimal haemophilia care produced in 2019 by three Working Groups (WG) on behalf of European Directorate for Quality of Medicines & Healthcare in the frame of the Kreuth V Initiative. WG1 recommended the access to prophylaxis for all patients, the attainment of plasma factor trough levels of at least 3-5% when extended half-life FVIII and FIX products are used, treatment regimen personalisation and choice of chromogenic assays for treatment monitoring. It was also emphasized that innovative therapies should be supervised by Haemophilia Comprehensive Care Ce...
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Peyvandi F, Berger K, Seitz R, Hilger A, Hecquet ML, Wierer M, Buchheit KH, O Mahony B, Bok A, Makris M, Mansmann U, Schramm W, Mannucci PM Tags: Haematologica Source Type: research

Evolutionary crossroads: morphological heterogeneity reflects divergent intra-clonal evolution in a case of high-grade B-cell lymphoma.
PMID: 32467139 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Tabanelli V, Melle F, Motta G, Mazzara S, Fabbri M, Corsini C, Gerbino E, Calleri A, Sapienza MR, Abbene I, Stufano V, Barberis M, Pileri SA Tags: Haematologica Source Type: research

An agenda for future research projects in polycythemia vera and essential thrombocythemia.
PMID: 32467140 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Barbui T, Vannucchi AM, Guglielmelli P, De Stefano V, Rambaldi A Tags: Haematologica Source Type: research

Anti-RhD antibody therapy modulates human natural killer cell function.
Abstract Anti-RhD antibodies are widely used in clinical practice to prevent immunization against RhD, principally in hemolytic disease of the fetus and newborn. Intriguingly, this disease is induced by production of the very same antibodies when an RhD negative woman is pregnant with an RhD positive fetus. Despite over five decades of use, the mechanism of this treatment is, surprisingly, still unclear. Here we show that anti-RhD antibodies induce human natural killer (NK) cell degranulation. Mechanistically, we demonstrate that NK cell degranulation is mediated by binding of the Fc segment of anti-RhD antibodies...
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Elias S, Kol I, Kahlon S, Amore R, Zeibak M, Mevorach D, Elchalal U, Zelig O, Mandelboim O Tags: Haematologica Source Type: research

Clinical spectrum and therapeutic management of auto-immune myelofibrosis: a nation-wide study of 30 cases.
J, Gottenberg JE, Korganow AS, Arnaud L, Martin T PMID: 32467142 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Mertz P, Chalayer E, Amoura Z, Cathebras P, Chiche L, Coestedoat N, Deroux A, Diot E, Durupt S, Forestier E, Gorse A, Hudier L, Killian M, Lambotte O, Lecomte C, Ledoult E, Martinez C, Mathian A, Morin AS, Noel N, Pineton De Chambrun M, Terriou L, Sibilia Tags: Haematologica Source Type: research

Anti-platelet properties of Pim kinase inhibition is mediated through disruption of thromboxane A2 receptor signalling.
We report for the first time that Pim-1 is expressed in human and mouse platelets. Genetic deletion or pharmacological inhibition of Pim kinase results in reduced thrombus formation but is not associated with impaired haemostasis. Attenuation of thrombus formation was found to be due to inhibition of the thromboxane A2 receptor as effects on platelet function was non-additive to inhibition caused by the cyclooxygenase inhibitor indomethacin or thromboxane A2 receptor antagonist GR32191. Treatment with Pim kinase inhibitors caused reduced surface expression of the thromboxane A2 receptor and resulted in reduced responses to...
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Unsworth AJ, Bye AP, Sage T, Gaspar RS, Eaton N, Drew C, Stainer A, Kriek N, Volberding PJ, Hutchinson JL, Riley R, Jones S, Mundell SJ, Cui W, Falet H, Gibbins JM Tags: Haematologica Source Type: research

Hemoglobin switching in mice carrying the Klf1Nan variant.
sen S Abstract Haploinsufficiency for transcription factor KLF1 causes a variety of human erythroid phenotypes, such as the In(Lu) blood type, increased HbA2 levels, and hereditary persistence of fetal hemoglobin. Severe dominant congenital dyserythropoietic anemia IV (OMIM 613673) is associated with the KLF1 p.E325K variant. CDA-IV patients display ineffective erythropoiesis and hemolysis resulting in anemia, accompanied by persistent high levels of embryonic and fetal hemoglobin. The mouse Nan strain carries a variant in the orthologous residue, KLF1 p.E339D. Klf1Nan causes dominant hemolytic anemia with many si...
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Korporaal A, Gillemans N, Heshusius S, Cantú I, van den Akker E, van Dijk TB, von Lindern M, Philipsen S Tags: Haematologica Source Type: research

Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.
This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies. PMID: 32467145 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - May 28, 2020 Category: Hematology Authors: Chiaretti S, Messina M, Della Starza I, Piciocchi A, Cafforio L, Cavalli M, Taherinasab A, Ansuinelli M, Elia L, Albertini Petroni G, La Starza R, Canichella M, Lauretti A, Puzzolo MC, Pierini V, Santoro A, Spinelli O, Apicella V, Capria S, Di Raimondo F, Tags: Haematologica Source Type: research

Myelodysplastic syndromes: moving towards personalized management.
g P Abstract The myelodysplastic syndromes (MDS) share an origin in the hematopoietic stem cell but have otherwise very heterogeneous biological and genetic characteristics. Clinical features are dominated by cytopenia and substantial risk for progression to acute myeloid leukemia. According to the World Health Organisation (WHO) MDS is defined by cytopenia, bone marrow dysplasia, and by certain karyotypic abnormalities. The understanding of disease pathogenesis has undergone major development with the implementation of next generation sequencing, and a closer integration of morphology, cytogenetics and molecular ...
Source: Haematologica - May 21, 2020 Category: Hematology Authors: Hellström-Lindberg E, Tobiasson M, Greenberg P Tags: Haematologica Source Type: research

A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia.
Abstract Leukocytes that lack HLA allelic expression are frequently detected in patients with acquired aplastic anemia (AA) who respond to immunosuppressive therapy (IST), although the exact mechanisms underlying the HLA loss and HLA allele repertoire likely to acquire loss-of-function mutations are unknown. We identified a common nonsense mutation at position 19 (c.19C>T, p.R7X) in exon 1 (Exon1mut ) of different HLA-A and -B alleles in HLA-lacking granulocytes from AA patients. A droplet digital PCR (ddPCR) assay capable of detecting as few as 0.07% Exon1mut HLA alleles in total DNA revealed the mutation was ...
Source: Haematologica - May 21, 2020 Category: Hematology Authors: Mizumaki H, Hosomichi K, Hosokawa K, Yoroidaka T, Imi T, Zaimoku Y, Katagiri T, Nguyen MAT, Tran DC, Elbadry MIY, Chonabayashi K, Yoshida Y, Takamatsu H, Ozawa T, Azuma F, Kishi H, Fujii Y, Ogawa S, Tajima A, Nakao S Tags: Haematologica Source Type: research

2'-O-methoxyethyl splice-switching oligos correct splicing from IVS2-745 β-thalassemia patient cells restoring HbA production and chain rebalance.
2'-O-methoxyethyl splice-switching oligos correct splicing from IVS2-745 β-thalassemia patient cells restoring HbA production and chain rebalance. Haematologica. 2020 May 21;: Authors: Dong A, Ghiaccio V, Motta I, Guo S, Peralta R, Freier SM, Watt A, Damle S, Ikawa Y, Jarocha D, Chappell M, Stephanou C, Delbini P, Chen C, Christou S, Kleanthous M, Smith-Whitley K, Manwani D, Casu C, Abdulmalik O, Cappellini MD, Rivella S, Breda L Abstract β-thalassemia is a disorder caused by altered hemoglobin protein synthesis and affects individuals worldwide. Severe forms of the disease, left untreated, ...
Source: Haematologica - May 21, 2020 Category: Hematology Authors: Dong A, Ghiaccio V, Motta I, Guo S, Peralta R, Freier SM, Watt A, Damle S, Ikawa Y, Jarocha D, Chappell M, Stephanou C, Delbini P, Chen C, Christou S, Kleanthous M, Smith-Whitley K, Manwani D, Casu C, Abdulmalik O, Cappellini MD, Rivella S, Breda L Tags: Haematologica Source Type: research

Thromboinflammatory mechanisms in sickle cell disease - challenging the hemostatic balance.
Abstract Sickle cell disease (SCD) is an inherited hemoglobinopathy that is caused by the presence of abnormal hemoglobin S (HbS) in red blood cells, leading to alterations in red cell properties and shape, as the result of HbS dexoygenation and subsequent polymerization. SCD pathophysiology is characterized by chronic inflammatory processes, triggered by hemolytic and vaso-occlusive events, which lead to the varied complications, organ damage and elevated mortality seen in individuals with the disease. In association with activation of the endothelium and leukocytes, hemostatic alterations and thrombotic events a...
Source: Haematologica - May 21, 2020 Category: Hematology Authors: Conran N, De Paula EV Tags: Haematologica Source Type: research