Significant hemolysis is not required for thrombosis in paroxysmal nocturnal hemoglobinuria.
PMID: 30287620 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 4, 2018 Category: Hematology Authors: Griffin M, Hillmen P, Munir T, Richards S, Arnold L, Riley K, Hill A Tags: Haematologica Source Type: research

Dyserythropoiesis evaluated by RED score and hepcidin/ferritin levels predicts response to erythropoietin in lower risk myelodysplastic syndromes.
, Rose C, Lachenal F, Toma A, Pica GM, Carre M, Garban F, Mariette C, Cahn JY, Meunier M, Herault O, Fenaux P, Wagner-Ballon O, Bardet V, Dreyfus F, Fontenay M Abstract Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in lower risk myelodysplastic syndrome patients. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including flow cytometry RED score, serum GDF-15, and hepcidin levels. Inclusion criteria were: Erythropoiesis stimulating agents naive, IPSS low or intermediate-1 MDS with Hemoglobin level4 (p=0.05)...
Source: Haematologica - October 4, 2018 Category: Hematology Authors: Park S, Kosmider O, Maloisel F, Drenou B, Chapuis N, Lefebvre T, Karim Z, Puy H, Alary AS, Ducamp S, Verdier F, Bouilloux C, Rousseau A, Jacob MC, Debliquis A, Charpentier A, Gyan E, Anglaret B, Leyronnas C, Corm S, Slama B, Cheze S, Laribi K, Amé S, Ros Tags: Haematologica Source Type: research

Improving consolidation therapy in acute myeloid leukemia - a tough nut to crack.
w C PMID: 30270203 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2018 Category: Hematology Authors: Schlenk RF, Jaramillo S, Müller-Tidow C Tags: Haematologica Source Type: research

Therapy-related acute lymphoblastic leukemia.
PMID: 30270204 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2018 Category: Hematology Authors: Ribera JM Tags: Haematologica Source Type: research

eGVHD App: a new tool to improve graft-versus-host disease assessment.
PMID: 30270205 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2018 Category: Hematology Authors: Rubio MT Tags: Haematologica Source Type: research

Infection prevention in patients with hereditary hemorrhagic telangiectasia.
, García-Erce JA PMID: 30270206 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2018 Category: Hematology Authors: Rodríguez-García J, Zarrabeitia-Puente R, Fernández-Santos R, García-Erce JA Tags: Haematologica Source Type: research

Infections and vaccination in hereditary hemorrhagic telangiectasia: microbiological evidence-based considerations.
PMID: 30270207 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2018 Category: Hematology Authors: Al-Samkari H, Kritharis A, Kuter DJ Tags: Haematologica Source Type: research

Transient decrease of serum iron after acute erythropoietin treatment contributes to hepcidin inhibition by ERFE in mice.
tri L PMID: 30266734 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 28, 2018 Category: Hematology Authors: Artuso I, Pettinato M, Nai A, Pagani A, Sardo U, Billoré B, Lidonnici MR, Bennett C, Mandelli G, Pasricha SR, Ferrari G, Camaschella C, Kautz L, Silvestri L Tags: Haematologica Source Type: research

Factor VIII cross-matches to the human proteome reduce the predicted inhibitor risk in missense mutation hemophilia A.
Abstract Single missense mutations in the F8 gene encoding the coagulation protein factor VIII (FVIII) give rise predominantly to non-severe hemophilia A. Despite only a single amino acid sequence difference between the replacement, therapeutic FVIII (tFVIII) and the patient's endogenous FVIII, tFVIII may still be perceived as foreign by the recipient's immune system and trigger an immune response (inhibitor). Inhibitor formation is a life-long risk for non-severe hemophilia A patients treated with tFVIII, but remains difficult to predict. The aim of this study was to understand whether fortuitous, primary sequenc...
Source: Haematologica - September 28, 2018 Category: Hematology Authors: Hart DP, Uzun N, Skelton S, Kakoschke A, Househam J, Moss DS, Shepherd AJ Tags: Haematologica Source Type: research

MiR-497 suppresses cycle progression through an axis involving CDK6 in ALK-positive cells.
Abstract Anaplastic large-cell lymphoma, a T cell neoplasm, is primarily a pediatric disease. 75% of pediatric anaplastic large-cell lymphoma cases harbor the chromosomal translocation t(2;5)(p23;q35) leading to the ectopic expression of NPM-ALK, a chimeric tyrosine kinase. NPM-ALK consists of an N-terminal nucleophosmin (NPM) domain fused to an anaplastic lymphoma kinase (ALK) cytoplasmic domain. Pediatric NPM-ALK(+) anaplastic large-cell lymphoma is often a disseminated disease and young patients are prone to chemoresistance or relapse shortly after chemotherapeutic treatment. Furthermore, there is no gold stand...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Hoareau-Aveilla C, Quelen C, Congras A, Caillet N, Labourdette D, Dozier C, Brousset P, Lamant L, Meggetto F Tags: Haematologica Source Type: research

Impaired factor XIII activation in patients with congenital afibrinogenemia.
Casini A PMID: 30262556 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Bridey F, Négrier C, Duval C, Ariëns R, de Moerloose P, Casini A Tags: Haematologica Source Type: research

Novel iatrogenic amyloidosis caused by peptide drug liraglutide: a clinical mimic of AL amyloidosis.
PMID: 30262557 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Martins CO, Lezcano C, Yi SS, Landau HJ, Chapman JR, Dogan A Tags: Haematologica Source Type: research

Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets.
Abstract High titers of HLA antibodies are associated with platelet refractoriness, causing poor platelet increments after transfusions in a subset of patients with HLA antibodies. Currently, we do not know the biological mechanisms that explain the variability in clinical responses in HLA alloimmunized patients receiving platelet transfusions. Previously we showed that a subset of anti-HLA IgG-antibodies induces FcγRIIa-dependent platelet activation and enhanced phagocytosis. Here we investigated whether anti-HLA IgG can induce complement activation on platelets. We found that a subset of anti-HLA IgG induc...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Rijkers M, Schmidt D, Lu N, Kramer CSM, Heidt S, Mulder A, Porcelijn L, Claas FHJ, Leebeek FWG, Jansen AJG, Jongerius I, Zeerleder SS, Vidarsson G, Voorberg J, de Haas M Tags: Haematologica Source Type: research

Highly sensitive methods are required to detect mutations in histiocytoses.
J, Emile JF PMID: 30262559 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Melloul S, Hélias-Rodzewicz Z, Cohen-Aubart F, Charlotte F, Fraitag S, Terrones N, Riller Q, Chazal T, Héritier S, Moreau A, Kambouchner M, Copin MC, Donadieu J, Taly V, Amoura Z, Haroche J, Emile JF Tags: Haematologica Source Type: research

Long term follow-up of tandem autologous-allogeneic hematopoietic cell transplantation for multiple myeloma.
Abstract We previously reported initial results in 102 multiple myeloma patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m2 and allogeneic hematopoietic cell transplantation. Here we present long-term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow-up of 8.3 (range 1.0-8.1) years. Donors included human leucocyte antigen identical siblings (n= 179) and HLA-matched unrelated donors (n= 65). A total of 209 patients (86%) received ta...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Maffini E, Storer BE, Sandmaier BM, Bruno B, Sahebi F, Shizuru JA, Chauncey TR, Hari P, Lange T, Pulsipher MA, McSweeney PA, Holmberg L, Becker PS, Green DJ, Mielcarek M, Maloney DG, Storb R Tags: Haematologica Source Type: research

Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia.
G, Peffault de Latour R, Sicre de Fontbrune F Abstract Aplastic anemia is a rare but potentially life-threatening disease that may affect older patients. Data regarding the treatment of aplastic anemia in this ageing population remains scarce. We conducted a retrospective nationwide multicenter study in France to examine current treatments for aplastic anemia patients over 60 years old. Our aims were to evaluate efficacy and tolerance, and to analyze predictive factors for response and survival. Over the course of a decade, 88 patients (median age 68.5) were identified in 19 centers, with a median follow-up of 2....
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Contejean A, Resche-Rigon M, Tamburini J, Alcantara M, Jardin F, Lengliné E, Adès L, Bouscary D, Marçais A, Lebon D, Chabrot C, Terriou L, Barraco F, Banos A, Bussot L, Cahn JY, Hirsch P, Maillard N, Simon L, Fornecker LM, Socié G, Peffault de Latour Tags: Haematologica Source Type: research

Rheb1 loss leads to increased hematopoietic stem cell proliferation and myeloid-biased differentiation in vivo.
Abstract Hematopoietic stem cells constitute a unique subpopulation of blood cells that have the ability to give rise to all types of mature cells in response to physiological demands. However, the intrinsic molecular machinery that regulates this transformative property remains elusive. In this paper, we demonstrate that small GTPase Rheb1 is a critical regulator of proliferation and differentiation of hematopoietic stem cells in vivo. Rheb1 deletion led to increased phenotypic hematopoietic stem cells/hematopoietic progenitor cells proliferation under the steady state condition. Over-proliferating Rheb1-deficien...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Wang X, Gao Y, Gao J, Li M, Zhou M, Wang J, Pang Y, Cheng H, Yuan C, Chu Y, Jiang Y, Zhou J, Luo HR, Ju Z, Cheng T, Yuan W Tags: Haematologica Source Type: research

ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells.
ico G Abstract B-cell precursor-Acute Lymphoblastic Leukemia modulates the bone marrow niche to become leukemia-supporting and chemoprotective by reprogramming the stromal microenvironment. New therapies targeting the leukemia/stroma interplay can be instrumental to improve disease outcome. We identified ActivinA, a TGF-β family member, with a well-described promoting role in several solid malignancies, as a new potentially targetable leukemia-favoring factor. ActivinA resulted overexpressed in the leukemic bone marrow and its production was strongly induced in mesenchymal stromal cells after culture with leu...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Portale F, Cricrì G, Bresolin S, Lupi M, Gaspari S, Silvestri D, Russo B, Marino N, Ubezio P, Pagni F, Vergani P, Te Kronnie G, Valsecchi MG, Locatelli F, Rizzari C, Biondi A, Dander E, D'Amico G Tags: Haematologica Source Type: research

Spatial clonal evolution leading to ibrutinib resistance and disease progression in chronic lymphocytic leukemia.
J, Mátrai Z, Bödör C PMID: 30262564 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Kiss R, Alpár D, Gángó A, Nagy N, Eyupoglu E, Aczél D, Matolcsy A, Csomor J, Mátrai Z, Bödör C Tags: Haematologica Source Type: research

T cell receptor alpha repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.
Schetelig J Abstract Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T cell receptor repertoire remains largely unknown. Using next generation sequencing, the T cell receptor alpha repertoire of naive and memory CD8+ T cells from 25 patients who had received different forms of allogeneic transplantation was analysed. In parallel, reconstitution of the CD8+/CD4+ T cell subsets was mapped using flow cytometry. When comparing the influence of anti-T c...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Link-Rachner CS, Eugster A, Rücker-Braun E, Heidenreich F, Oelschlägel U, Dahl A, Klesse C, Kuhn M, Middeke JM, Bornhäuser M, Bonifacio E, Schetelig J Tags: Haematologica Source Type: research

B-lymphoblastic lymphoma with the TCF3-PBX1 fusion gene.
PMID: 30262566 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Kubota-Tanaka M, Osumi T, Miura S, Tsujimoto H, Imamura T, Nishimura A, Oki K, Nakamura K, Miyamoto S, Inoue K, Inoue M, Kamiya T, Yanagimachi M, Okano T, Mitsuiki N, Isoda T, Imai K, Kanegane H, Morio T, Kounami S, Endo M, Kato M, Takagi M Tags: Haematologica Source Type: research

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia.
In conclusion, the relative weight of indicators that can accurately risk stratify early-stage chronic lymphocytic leukemia patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in chronic lymphocytic leukemia. PMID: 30262567 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Baliakas P, Moysiadis T, Hadzidimitriou A, Xochelli A, Jeromin S, Agathangelidis A, Mattsson M, Sutton LA, Minga E, Scarfò L, Rossi D, Davis Z, Villamor N, Parker H, Kotaskova J, Stalika E, Plevova K, Mansouri L, Cortese D, Navarro A, Delgado J, Larrayoz Tags: Haematologica Source Type: research

Mutations in RAS-BRAF-MAPK-ERK pathway define a specific subgroup of patients with adverse clinical features and provide new therapeutic options in chronic lymphocytic leukemia.
In conclusion, although larger series of patients are needed to corroborate these findings, our results suggest that RAS-BRAF-MAPK-ERK pathway is one of the core cellular processes affected by novel mutations in chronic lymphocytic leukemia, it is associated with adverse clinical features and it could be pharmacologically inhibited. PMID: 30262568 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Giménez N, Martínez-Trillos A, Montraveta A, Lopez-Guerra M, Rosich L, Nadeu F, Valero JG, Aymerich M, Magnano L, Rozman M, Matutes E, Delgado J, Bauman T, Gine E, González M, Alcoceba M, Terol MJ, Navarro B, Colado E, Payer AR, Puente XS, López-Otín Tags: Haematologica Source Type: research

The high NRF2 expression confers chemotherapy resistance partly through up-regulated DUSP1 in myelodysplastic syndromes.
In conclusion, our study suggests that targeting NFE2L2 in combination with conventional chemotherapy could pave the way for future high-risk myelodysplastic syndromes therapy. PMID: 30262569 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Lin P, Ren Y, Yan X, Luo Y, Zhang H, Kesarwani M, Bu J, Zhan D, Zhou Y, Tang Y, Zhu S, Xu W, Zhou X, Mei C, Ma L, Ye L, Hu C, Azam M, Ding W, Jin J, Huang G, Tong H Tags: Haematologica Source Type: research

THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during inudction therapy of acute lymphoblastic leukemia in children and adolescents.
ricke A Abstract Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared efficacy and safety of antithrombotic interventions in the consecutive leukemia trials ALL-BFM 2000 and AIEOP-BFM ALL 2009. Patients with newly diagnosed acute lymphoblastic leukemia (n=949, age 1 to 18 years) were randomized to receive low-dose unfractionated heparin, prophylactic low-molecular-weight heparin (enoxaparin) or activity-adapted antithrombin throughout induction therapy. Primary objective was to test whether enoxaparin or antithrombin reduce the inciden...
Source: Haematologica - September 27, 2018 Category: Hematology Authors: Greiner J, Schrappe M, Claviez A, Zimmermann M, Niemeyer C, Kolb R, Eberl W, Berthold F, Bergsträsser E, Gnekow A, Lassay E, Vorwerk P, Lauten M, Sauerbrey A, Rischewski J, Beilken A, Henze G, Korte W, Möricke A Tags: Haematologica Source Type: research

Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis.
We report that regardless of risk-group, bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients support, similar to those derived from healthy bone-marrow the survival, proliferation, differentiation and clonogenecity of CD34+ cells in vitro, and the in vivo immune deficient mice repopulating assays. Additionally, bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients were capable of reversing the inflammatory phenotype in preclinical models of acute severe colitis, showing a greater anti-inflammatory capacity compared to those derived from healthy bone marrow. Collectively...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Díaz de la Guardia R, Lopez-Millan B, Roca-Ho H, Bueno C, Gutiérrez-Agüera F, Luis Fuster J, Anguita E, Zanetti S, Vives S, Nomdedeu J, Sackstein R, Lavoie J, Gónzalez-Rey E, Delgado M, Rosu-Myles M, Menendez P Tags: Haematologica Source Type: research

The allo-HLA-DP restricted T cell repertoire provoked by allogeneic dendritic cells contains T cells that show restricted recognition of hematopoietic cells including primary malignant cells.
In this study we elucidated that the allo-HLA-DP restricted T cell repertoire contained T cells with differential cell-lineage-specific recognition profiles. As expected, part of the allo-HLA-DP restricted T cells showed broad recognition of a variety of hematopoietic and non-hematopoietic cell types expressing the targeted mismatched HLA-DP allele. However, a significant proportion of the allo-HLA-DP restricted T cells showed restricted recognition of hematopoietic cells, including primary malignant cells, or even restricted recognition of only myeloid cells, including dendritic cells and primary acute-myeloid-leukemia sa...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Laghmouchi A, Hoogstraten C, Van Balen P, Falkenburg JHF, Jedema I Tags: Haematologica Source Type: research

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX.
u K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ Abstract In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow-up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow-up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; ha...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O' Rourke L, Tags: Haematologica Source Type: research

Clonally related diffuse large B-cell lymphoma and interdigitating dendritic cell sarcoma sharing MYC translocation.
PMID: 30237263 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Ochi Y, Hiramoto N, Yoshizato T, Ono Y, Takeda J, Shiozawa Y, Yoshida K, Kakiuchi N, Shiraishi Y, Tanaka H, Chiba K, Kazuma Y, Tabata S, Yonetani N, Uehara K, Yamashita D, Imai Y, Nagafuji K, Yamakawa M, Miyano S, Takaori-Kondo A, Ogawa S, Ishikawa T Tags: Haematologica Source Type: research

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.
Jo JC, Shin HJ, Sonneveld P, Soong D, Casneuf T, Chiu C, Amin H, Qi M, Thiyagarajah P, Sasser AK, Schecter JM, Mateos MV Abstract Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow-up is presented. After 19.4 (range: 0 to 27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone prolonged progression-fre...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Spencer A, Lentzsch S, Weisel K, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka AK, Quach H, Lee C, Barreto W, Corradini P, Min CK, Scott EC, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Tags: Haematologica Source Type: research

Machine learning reveals chronic graft-versus-host disease phenotypes and stratifies survival after stem cell transplant for hematologic malignancies.
Abstract The application of machine learning in medicine has been productive in multiple fields, and has not previously been applied to analyze the complexity of chronic graft-versus-host disease organ involvement. Chronic graft-versus-host disease is classified by an overall composite score of mild, moderate or severe, which may overlook clinically relevant patterns in organ involvement. Here we applied a novel computational approach to chronic graft-versus-host disease with the goal of identifying phenotypic groups based on the subcomponents of the National Institutes of Health (NIH) Consensus Criteria. Computat...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Gandelman JS, Byrne MT, Mistry AM, Polikowsky HG, Diggins KE, Chen H, Lee SJ, Arora M, Cutler C, Flowers M, Pidala J, Irish JM, Jagasia MH Tags: Haematologica Source Type: research

Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life.
h R Abstract Despite significantly improved survival and response rates in patients diagnosed with multiple myeloma, it still remains an incurable disease with a poor outcome especially in high-risk groups. Allogeneic stem cell transplantation offers a potentially curative option but is discussed controversially due to considerable treatment related toxicity. We analyzed 109 consecutive myeloma patients who received reduced-intensity conditioning allogeneic transplantation at the Freiburg University Medical Center between 2000 and 2017. Although most patients were heavily pretreated in high-risk constellations, th...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Greil C, Engelhardt M, Ihorst G, Schoeller K, Bertz H, Marks R, Zeiser R, Duyster J, Einsele H, Finke J, Wäsch R Tags: Haematologica Source Type: research

A gain of function variant in PIEZO1 (E756del) and sickle cell disease.
PMID: 30237267 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Rooks H, Brewin J, Gardner K, Chakravorty S, Menzel S, Hannemann A, Gibson J, Rees DC Tags: Haematologica Source Type: research

Transglutaminase 2 programs differentiating acute promyelocytic leukemia cells in all-trans retinoic acid treatment to inflammatory stage through NF-kB activation.
This study demonstrates that transglutaminase 2 expression induced by all-trans retinoic acid treatment reprograms inflammatory signaling networks governed by nuclear factor kappa-light-chain-enhancer of activated B cells activation, resulting in over-expression of tumor necrosis factor alpha and Interleukin 1 beta in differentiating acute promyelocytic leukemia cells, suggesting that atypically expressed transglutaminase 2 is a promising target for leukemia treatment. PMID: 30237268 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Jambrovics K, Uray IP, Keressztesy Z, Keillor JW, Fésüs L, Balajthy Z Tags: Haematologica Source Type: research

A novel gain-of-function mutation of Piezo1 is functionally affirmed in red blood cells by high-throughput patch clamp.
aestner L PMID: 30237269 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Rotordam GM, Fermo E, Becker N, Barcellini W, Brüggemann A, Fertig N, Egée S, Rapedius M, Bianchi P, Kaestner L Tags: Haematologica Source Type: research

Somatic mosaicisms of chromosome 1 at two different stages of ontogenetic development detected by Rh blood group discrepancies.
;rmöczi GF Abstract Spontaneous Rh blood group changes are a striking sign, reported to occur preferably in patients with hematological disorders. Upon routine blood grouping, two unrelated individuals showed unexplained mixed red cell phenotype regarding the highly immunogenic c antigen (RH4) clinically relevant for blood transfusion and fetomaternal incompatibility. About half of their red cells were c-positive, whereas the other half was c-negative. These apparently hematologically healthy females had no history of transfusion or transplantation, and they tested negative for chimerism. Genotyping of flanki...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Dauber EM, Mayr WR, Hustinx H, Schönbacher M, Budde H, Legler TJ, König M, Haas OA, Fritsch G, Körmöczi GF Tags: Haematologica Source Type: research

T-cell inflamed tumor microenvironment predicts favorable prognosis in primary testicular lymphoma.
auml; S Abstract Primary testicular lymphoma is a rare lymphoid malignancy, most often representing diffuse large B-cell lymphoma histologically. Tumor microenvironment and limited immune surveillance have a major impact on diffuse large B-cell lymphoma pathogenesis and survival, but the impact on primary testicular lymphoma is unknown. Here, the purpose was to characterize tumor microenvironment in primary testicular lymphoma, and associate the findings with outcome. We profiled the expression of 730 immune response genes in 60 primary testicular lymphomas utilizing Nanostring platform, and used multiplex immunoh...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Leivonen SK, Pollari M, Brück O, Pellinen T, Autio M, Karjalainen-Lindsberg ML, Mannisto S, Kellokumpu-Lehtinen PL, Kallioniemi O, Mustjoki S, Leppä S Tags: Haematologica Source Type: research

Clinical and molecular features of acute promyelocytic leukemia with variant retinoid acid receptor fusions.
PMID: 30237272 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Wen L, Xu Y, Yao L, Wang N, Wang Q, Liu T, Pan J, Cen J, Zhou H, Miao M, Shao YW, Wang X, Wang X, Ruan C, Wu D, Chen S Tags: Haematologica Source Type: research

T cell large granular lymphocytic leukemia and plasma cell disorders.
PMID: 30237273 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Sidiqi MH, Aljama MA, Viswanatha DS, Dingli D Tags: Haematologica Source Type: research

Hypersensitivity reactions to asparaginase in mice are mediated by anti-asparaginase IgE and IgG and the immunoglobulin receptors Fc ϵRI and FcγRIII.
Hypersensitivity reactions to asparaginase in mice are mediated by anti-asparaginase IgE and IgG and the immunoglobulin receptors FcϵRI and FcγRIII. Haematologica. 2018 Sep 20;: Authors: Rathod S, Ramsey M, Relling MV, Finkelman FD, Fernandez CA Abstract Asparaginase is an important drug for the treatment of leukemias. However, anti-asparaginase antibodies often develop, which can decrease asparaginase drug levels and increase the risk of relapse. The aim of this study is to identify the immunoglobulin isotypes and receptors responsible for asparaginase hypersensitivities. Mice immunized with a...
Source: Haematologica - September 20, 2018 Category: Hematology Authors: Rathod S, Ramsey M, Relling MV, Finkelman FD, Fernandez CA Tags: Haematologica Source Type: research

JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte rich large B-cell lymphoma.
n S Abstract T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma showing histopathological overlap with nodular lymphocyte predominant Hodgkin lymphoma. Despite differences in tumor microenvironment and clinical behavior, the tumor cells of both entities show remarkable similarities, suggesting that both lymphomas might represent a spectrum of the same disease. To address this issue, we investigated if these entities share mutations. Ultra-deep targeted resequencing of 6 typical and 11 histopathological variants of nodular lymphocyte predominant Hodgkin lymphoma, and 9 T-cell/histiocyte-rich...
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Schuhmacher B, Bein J, Rausch T, Benes V, Tousseyn T, Vornanen M, Ponzoni M, Thurner L, Gascoyne R, Steidl C, Küppers R, Hansmann ML, Hartmann S Tags: Haematologica Source Type: research

TLR7 ligand R848 prevents mouse graft-versus-host disease and cooperates with anti-IL-27 antibody for maximal protection and Treg upregulation.
Abstract In spite of considerable therapeutic progress, acute graft-versus-host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested pharmacologic TLR7 ligand R848 in this model and observed complete survival if donor and recipients were treated before transplantation. Mixed lymphocyte culture performed 48 h after R848-treatment of normal mice demonstrated that both T cell allo-responsi...
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Gaignage M, Marillier RG, Cochez PM, Dumoutier L, Uyttenhove C, Coutelier JP, Van Snick J Tags: Haematologica Source Type: research

Long non-coding RNA NEAT1 shows high expression unrelated to molecular features and clinical outcome in multiple myeloma.
PMID: 30213829 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Taiana E, Ronchetti D, Favasuli V, Todoerti K, Manzoni M, Amodio N, Tassone P, Agnelli L, Neri A Tags: Haematologica Source Type: research

Somatic reversion events point towards RPL4 as a novel disease gene in a condition resembling Diamond-Blackfan Anemia.
PMID: 30213830 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Jongmans MCJ, Diets IJ, Quarello P, Garelli E, Kuiper RP, Pfundt R Tags: Haematologica Source Type: research

Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study.
ranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Verhovsek M, Kunz J, McNaull MA, Rose MJ, Bradeen HA, Addonizio K, Li A, Al-Sayegh H, London WB, Grace RF PMID: 30213831 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 13, 2018 Category: Hematology Authors: van Beers EJ, van Straaten S, Morton DH, Barcellini W, Eber SW, Glader B, Yaish HM, Chonat S, Kwiatkowski JL, Rothman JA, Sharma M, Neufeld EJ, Sheth S, Despotovic JM, Kollmar N, Pospisilova D, Knoll CM, Kuo K, Pastore YD, Thompson AA, Newburger PE, Ravin Tags: Haematologica Source Type: research

Long-term follow-up of Pediatric Philadelphia Positive Acute Lymphoblastic Leukemia treated with the EsPhALL2004 study: high white blood cell count at diagnosis is the strongest prognostic factor.
PMID: 30213832 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Biondi A, Cario G, De Lorenzo P, Castor A, Conter V, Leoni V, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Attarbaschi A, Li CK, Vora A, Bradtke J, Saha V, Valsecchi MG, Schrappe M Tags: Haematologica Source Type: research

Exposure to non-inherited maternal antigens by breastfeeding affects antibody responsiveness.
Abstract The observation, by Ray Owen and colleagues in 1954, that D-negative women were less likely to form anti-D antibodies against their D-positive fetus if their mother possessed the D-antigen, was not found in all later studies. We hypothesized that breastfeeding, received by the mother, may affect her immunity against non-inherited maternal red blood cell antigens. We studied a cohort of 125 grandmother-mother-child combinations, from a follow-up study of mothers after intrauterine transfusion of the fetus for alloimmune hemolytic disease. For mismatched red blood cell antigens the mother was exposed to, wh...
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Schonewille H, van Rood JJ, Verduin EP, van de Watering LMG, Haasnoot GW, Claas FHJ, Oepkes D, Lopriore E, Brand A Tags: Haematologica Source Type: research

Treatment outcomes and prognostic factors of adult patients with non-malignancy associated secondary hemophagocytic lymphohistiocytosis.
Abstract Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors of secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved complete response at 4 weeks were defined as early-stable responders, those who failed to achieve complete response but showed continuous improvement until 8 weeks as late responders, those...
Source: Haematologica - September 13, 2018 Category: Hematology Authors: Yoon JH, Park SS, Jeon YW, Lee SE, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Lee JW Tags: Haematologica Source Type: research

Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy.
PMID: 30190341 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 6, 2018 Category: Hematology Authors: Eyre TA, Walter HS, Iyengar S, Follows G, Cross M, Fox CP, Hodson A, Coats J, Narat S, Morley N, Dyer MJS, Collins GP Tags: Haematologica Source Type: research

Prognostic implications of additional genomic lesions in adult Ph+ acute lymphoblastic leukemia.
tti S Abstract To shed light into the molecular basis of Ph+ acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult Ph+ acute lymphoblastic leukemia patients enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that Ph+ acute lymphoblastic leukemia patients carry 7.8 lesions/case on average, with deletions outnumbering gains (88% vs 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B detec...
Source: Haematologica - September 6, 2018 Category: Hematology Authors: Fedullo AL, Messina M, Elia L, Piciocchi A, Gianfelici V, Lauretti A, Soddu S, Puzzolo MC, Minotti C, Ferrara F, Martino B, Chiusolo P, Calafiore V, Paolini S, Vignetti M, Vitale A, Guarini A, Foà R, Chiaretti S Tags: Haematologica Source Type: research