Sequential and combination treatments with novel agents in chronic lymphocytic leukemia.
t B Abstract Chemoimmunotherapy has been standard of care in patients with chronic lymphocytic leukemia for a long time. Over the last years, novel agents have produced unprecedented outcomes in treatment-naive and relapsed/refractory chronic lymphocytic leukemia. With the advent of these targeted agents, treatment options have extensively diversified and new questions emerge. It is still unclear whether these novel agents should be used as sequential monotherapies until disease progression or if they should preferably be combined in time-limited treatment regimens aiming at deep and durable remissions. While both...
Source: Haematologica - October 4, 2019 Category: Hematology Authors: Fürstenau M, Hallek M, Eichhorst B Tags: Haematologica Source Type: research

Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients.
Abstract In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission of danger signals in the form of damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates that danger signals play a crucial role in the (re-)activation of antitumor immune responses in vivo, thus having a major impact on patient prognosis. We have previously demonstrated that the presence of calreticulin on the surface of malignant blasts is a positive prognostic biomarker for patients with acute myeloid leukemia. Calreticulin...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Truxova I, Kasikova L, Salek C, Hensler M, Lysak D, Holicek P, Bilkova P, Holubova M, Chen X, Mikyskova R, Reinis M, Kovar M, Tomalova B, Kline JP, Galluzzi L, Spisek R, Fucikova J Tags: Haematologica Source Type: research

Identification of PIKfyve kinase as a target in multiple myeloma.
Abstract The cellular cytotoxicity of APY0201, a PIKfyve inhibitor, against multiple myeloma was initially identified in an unbiased in vitro chemical library screen. Activity was confirmed in all 25 cell lines tested and 40% of 100 ex vivo patient derived primary samples, and positively correlated with samples harboring trisomies and inversely related to t(11;14). The broad anti- multiple myeloma activity of PIKfyve inhibitors was further demonstrated in confirmatory screens and showed the superior potency of APY0201 when compared to the PIKfyve inhibitors YM201636 and apilimod, with a mid-point EC50 at nanomolar...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Bonolo De Campos C, Zhu YX, Sepetov N, Romanov S, Bruins LA, Shi CX, Stein CK, Petit JL, Polito AN, Sharik ME, Meermeier EW, Ahmann GJ, Lopez Armenta ID, Kruse J, Bergsagel PL, Chesi M, Meurice N, Braggio E, Stewart AK Tags: Haematologica Source Type: research

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma.
berg LS Abstract Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom were previously treated for Hodgkin lymphoma. To investigate MKL1 and B cell responses in HL pathogenesis, we generated Epstein Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the Hodgkin lymphoma tre...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Record J, Sendel A, Kritikou JS, Kuznetsov NV, Brauner H, He M, Nagy N, Oliveira MMS, Griseti E, Haase CB, Dahlström J, Boddul S, Wermeling F, Thrasher AJ, Liu C, Andersson J, Claesson HE, Winqvist O, Burns SO, Björkholm M, Westerberg LS Tags: Haematologica Source Type: research

IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study.
Abstract Patients with chronic lymphocytic leukemia and immunoglobulin heavy-chain variable region gene unmutated status have inferior survival from time of treatment in clinical studies. We assessed real-world outcomes based on mutational status and treatment regimen in a nationwide population-based cohort, comprising all 4135 patients from the Danish chronic lymphocytic leukemia registry diagnosed between 2008 and 2017. In total, 850 patients with known mutational status received treatment: 42% of patients received intensive chemoimmunotherapy treatment consisting of fludarabine, cyclophosphamide plus rituximab,...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Rotbain EC, Frederiksen H, Hjalgrim H, Rostgaard K, Jakupsdottir Egholm G, Zahedi B, Poulsen CB, Enggaard L, da Cunha-Bang C, Niemann CU Tags: Haematologica Source Type: research

A high-content cytokine screen identifies myostatin propeptide as a positive regulator of primitive chronic myeloid leukemia cells.
ng;s M, Fioretos T Abstract Aberrantly expressed cytokines in the bone marrow niche are increasingly recognized as critical mediators of survival and expansion of leukemic stem cells. To identify regulators of primitive chronic myeloid leukemia cells, we performed a high-content cytokine screen using primary CD34+ CD38low chronic phase choric myeloid leukemia cells. Out of the 313 unique human cytokines evaluated, 11 were found to expand cell numbers ≥ 2-fold in a 7-day culture. Focusing on novel positive regulators of primitive chronic myeloid leukemia cells, the myostatin antagonist myostatin propeptide gave ...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: von Palffy S, Landberg N, Sandén C, Zacharaki D, Shah M, Nakamichi N, Hansen N, Askmyr M, Lilljebjörn H, Rissler M, Karlsson C, Scheding S, Richter J, Eaves CJ, Bhatia R, Järås M, Fioretos T Tags: Haematologica Source Type: research

Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial.
Hájek R, Boccadoro M, Larocca A Abstract In the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction has been prospectively evaluated in transplant-ineligible multiple myeloma patients. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. This analysis (median follow-up of 71 months) focused on maintenance treatment and on subgroup analyses according to the International Myeloma Working Group Frailty Score. 217 patients in lenalidomide-dexamethasone, 217 in melphalan-predniso...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Bringhen S, D'Agostino M, Paris L, Ballanti S, Pescosta N, Spada S, Pezzatti S, Grasso M, Rota-Scalabrini D, De Rosa L, Pavone V, Gazzera G, Aquino S, Poggiu M, Santoro A, Gentile M, Baldini L, Petrucci MT, Tosi P, Marasca R, Cellini C, Palumbo A, Falco P Tags: Haematologica Source Type: research

Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult beta-thalassemia major.
Abstract Minihepcidins are hepcidin agonists that have been previously shown to reverse iron overload and improve erythropoiesis in mice affected by non-transfusion dependent thalassemia. Due to their extreme anemia, the previous model of transfusion dependent thalassemia is inadequate to investigate whether Minihepcidins can improve red blood cell quality, lifespan and, ineffective erythropoiesis. To overcome this limitation, we generated a new murine model of transfusion dependent thalassemia with severe anemia and splenomegaly, but sufficient red cells and hemoglobin production to test the effect of Minihepcidi...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Casu C, Chessa R, Liu A, Gupta R, Drakesmith H, Fleming R, Ginzburg YZ, MacDonald B, Rivella S Tags: Haematologica Source Type: research

Multiple myeloma exploits Jagged1 and Jagged2 to promote intrinsic and bone marrow-dependent drug resistance.
Abstract Multiple myeloma is still incurable due to an intrinsic aggressiveness or, more frequently, to the interactions of malignant plasma cells with bone marrow microenvironment. Myeloma cells educate bone marrow cells to support neoplastic cell growth, survival, acquisition of drug resistance resulting in disease relapse. Myeloma microenvironment is characterized by Notch signaling hyperactivation due to the increased expression of Notch1 and 2 and the ligands Jagged1 and 2 in tumor cells. Notch activation influences myeloma cell biology and promotes the reprogramming of bone marrow stromal cells. In this work...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Colombo M, Garavelli S, Mazzola M, Platonova N, Giannandrea D, Colella R, Apicella L, Lancellotti M, Lesma E, Ancona S, Palano MT, Barbieri M, Taiana E, Lazzari E, Basile A, Turrini M, Pistocchi A, Neri A, Chiaramonte R Tags: Haematologica Source Type: research

Coactosin-like 1 integrates signaling critical for shear-dependent thrombus formation in mouse platelets.
Abstract Platelet aggregate formation is a multistep process involving receptor-mediated, as well as biomechanical signaling cascades, which are highly dependent on actin dynamics. We have previously shown that actin depolymerizing factor (ADF)/n-cofilin and Twinfilin 2a, members of the ADF homology (ADF-H) protein family, have distinct roles in platelet formation and function. Coactosin-like 1 (Cotl1) is another ADF-H protein that binds actin and was additionally shown to enhance biosynthesis of pro-inflammatory leukotrienes (LTs) in granulocytes. Here, we generated mice lacking Cotl1 in the megakaryocyte lineage...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Scheller I, Stritt S, Beck S, Peng B, Pleines I, Heinze KG, Braun A, Otto O, Ahrends R, Sickmann A, Bender M, Nieswandt B Tags: Haematologica Source Type: research

Clonal hematopoiesis in patients with ANCA-associated vasculitis.
Abstract PMID: 31582546 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Arends CM, Weiss M, Christen F, Eulenberg-Gustavus C, Rousselle A, Kettritz R, Eckardt KU, Chan W, Hoyer K, Frick M, Bullinger L, Bieringer M, Schreiber A, Damm F Tags: Haematologica Source Type: research

A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.
We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count>32.0x103/microliter, 1 point. L...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Cohen JA, Rossi FM, Zucchetto A, Bomben R, Terzi-di-Bergamo L, Rabe KG, Degan M, Steffan A, Polesel J, Santinelli E, Innocenti I, Cutrona G, D' Arena G, Pozzato G, Zaja F, Chiarenza A, Rossi D, Di Raimondo F, Laurenti L, Gentile M, Morabito F, Neri A, Fer Tags: Haematologica Source Type: research

How I diagnose and manage Philadelphia chromosome-like acute lymphoblastic leukemia.
Abstract Advances in our understanding of mechanisms of leukemogenesis and driver mutations in acute lymphoblastic leukemia lead to a more precise and informative sub-classification, mainly of B-acute lymphoblastic leukemia. In parallel, in recent years, novel agents have been approved for B-acute lymphoblastic leukemia therapy, and many others are in active clinical research. Among the newly recognized disease subtypes, Philadelphia-chromosome-like acute lymphoblastic leukemia is most heterogeneous and thus, diagnostically challenging. Given that this B-acute lymphoblastic leukemia subtype is associated with a po...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Frisch A, Ofran Y Tags: Haematologica Source Type: research

Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globuline, cyclosporine, with or without G-CSF: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation.
stic Anemia Working Party of the European Society for Blood and Marrow Transplantation Abstract This follow-up study of the randomized prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving Antithymoglobulin and Cyclosporine, with and without G-CSF. We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome or acute myeloid leukemia, clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (10.9-12.5). Overal...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Tichelli A, Peffault de Latour R, Passweg J, Knol-Bout C, Socié G, Marsh J, Schrezenmeier H, Höchsmann B, Bacigalupo A, Samarasinghe S, Rovó A, Kulasekararaj A, Röth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C, Severe Aplastic Anemia Working Tags: Haematologica Source Type: research

Linkage analysis combined with whole exome sequencing identifies a novel prothrombin (F2) gene mutation in a Dutch Caucasian family with unexplained thrombosis.
Abstract PMID: 31582550 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Mulder R, Lisman T, Meijers JCM, Huntington JA, Mulder AB, Meijer K Tags: Haematologica Source Type: research

Inflammation regulates long non-coding RNA-PTTG1-1:1 in myeloid leukemia.
Diederich M Abstract PMID: 31582551 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Chateauvieux S, Gaigneaux A, Gérard D, Orsini M, Morceau F, Orlikova-Boyer B, Farge T, Récher C, Sarry JE, Dicato M, Diederich M Tags: Haematologica Source Type: research

Kikuchi-Fujimoto disease and breast implants: is there a relationship?
ué O Abstract PMID: 31582552 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Sangiorgio V, Veloza L, Galvis K, López M, Frigola G, Campo E, Balagué O Tags: Haematologica Source Type: research

Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia.
In conclusion, the combination of 90Y-DOTA-BC8 with an allogeneic hematopoietic cell transplantation regimen was feasible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease. Clinicaltrials.gov identifier: NCT01300572. PMID: 31582553 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Vo P, Gooley TA, Rajendran JG, Fisher DR, Orozco JJ, Green DJ, Gopal AK, Haaf R, Nartea M, Storb R, Appelbaum FR, Press OW, Pagel JM, Sandmaier BM Tags: Haematologica Source Type: research

Fibrinogen gamma gene rs2066865 and risk of cancer-related venous thromboembolism.
In conclusion, homozygosity at the FGG variant and active cancer yielded synergistic effect on the risk of venous thromboembolism. PMID: 31582554 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Paulsen B, Skille H, Smith EN, Hveem K, Gabrielsen ME, Brækkan SK, Rosendaal FR, Frazer KA, Gran OV, Hansen JB Tags: Haematologica Source Type: research

Clonal tracking of erythropoiesis in rhesus macaques.
Abstract The classical model of hematopoietic hierarchies is being reconsidered, based on data from in vitro assays and single cell expression profiling. Recent experiments suggested that the erythroid lineage might differentiate directly from multipotent hematopoietic stem cells/ progenitors or from a highly biased subpopulation of stem cells, rather than transiting through common myeloid progenitors or megakaryocyte-erythrocyte progenitors. We genetically barcoded autologous rhesus macaque stem and progenitor cells, allowing quantitative tracking of the in vivo clonal output of thousands of individual cells over...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Fan X, Wu C, Truitt LL, Espinoza DA, Sellers S, Bonifacino A, Zhou Y, Cordes SF, Krouse A, Metzger M, Donahue RE, Lu R, Dunbar CE Tags: Haematologica Source Type: research

The dynamic emergence of GATA1 complexes identified in in vitro ES differentiation and in vivo mouse fetal liver.
Abstract GATA1 is an essential transcriptional regulator of myeloid hematopoietic differentiation towards red blood cells. During erythroid differentiation, GATA1 forms different complexes with other transcription factors such as LDB1, TAL1, E2A and LMO2 'he LDB1 complex') or with FOG1. The functions of GATA1 complexes have been studied extensively in definitive erythroid differentiation; however, the temporal and spatial formation of these complexes during erythroid development is unknown. We applied proximity ligation assay (PLA) to detect, localize and quantify individual interactions during ES cell differentia...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Yu X, Martella A, Kolovos P, Stevens M, Stadhouders R, Grosveld FG, Andrieu-Soler C Tags: Haematologica Source Type: research

Safety of using direct oral anticoagulants in the diagnostic workup of outpatients with suspicion of acute venous thromboembolism.
Abstract PMID: 31582557 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Stephen MS, Catellucci L, Carrier M, Duffett L, Le Gal G, Rodger M, Wells PS, Delluc A Tags: Haematologica Source Type: research

The stromal microenvironment provides an escape route from FLT3 inhibitors through the GAS6-AXL-STAT5 axis.
PMID: 31575669 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: Orlova A, Neubauer HA, Moriggl R Tags: Haematologica Source Type: research

Pediatric aplastic anemia treatment patterns and responses; power in the numbers.
PMID: 31575670 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: Fox LC, Ritchie DS Tags: Haematologica Source Type: research

p66Shc deficiency sets the scene for clinically aggressive chronic lymphocytic leukemia.
PMID: 31575671 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: Rosenquist R Tags: Haematologica Source Type: research

Hereditary thrombotic thrombocytopenic purpura.
PMID: 31575672 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: Scully M Tags: Haematologica Source Type: research

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population.
-Göttl U PMID: 31575673 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: deVeber G, Kirkham F, Shannon K, Brandão L, Sträter R, Kenet G, Clausnizer H, Moharir M, Kausch M, Askalan R, MacGregor D, Stoll M, Torge A, Dlamini N, Ganesan V, Prengler M, Singh J, Nowak-Göttl U Tags: Haematologica Source Type: research

IGHV1 status in chronic lymphocytic leukemia identify ethnic groups with an aggressive clinical course (Comment to Giudice ID, Fo à R. Haematologica. 2019;104(2):219-221).
IGHV1 status in chronic lymphocytic leukemia identify ethnic groups with an aggressive clinical course (Comment to Giudice ID, Foà R. Haematologica. 2019;104(2):219-221). Haematologica. 2019 Oct;104(10):e493 Authors: Amato T, Granai M, Leoncini L, Bellan C PMID: 31575674 [PubMed - in process] (Source: Haematologica)
Source: Haematologica - October 1, 2019 Category: Hematology Authors: Amato T, Granai M, Leoncini L, Bellan C Tags: Haematologica Source Type: research

Myeloid neoplasms with isolated del(5q) and JAK2 V617F mutation: a grey zone combination of myelodysplastic and myeloproliferative features?
Abstract PMID: 31558664 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Sangiorgio VF, Geyer JT, Margolskee E, Al-Kawaaz M, Mathew S, Tam W, Orazi A Tags: Haematologica Source Type: research

Functional assessment of glucocerebrosidase modulator efficacy in primary patient-derived macrophages is essential for drug development and patient stratification.
Abstract PMID: 31558665 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Welsh NJ, Gewinner CA, Mistry K, Koglin M, Cooke J, Butler M, Powney B, Roberts M, Staddon JM, Schapira AHV Tags: Haematologica Source Type: research

IKZF1/3 and CRL4-CRBN E3 ubiquitin ligase mutations and IMiD resistance in multiple myeloma.
Einsele H, Stühmer T, Kortüm KM Abstract PMID: 31558666 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Barrio S, Munawar U, Zhu YX, Giesen N, Shi CX, Da Viá M, Sanchez R, Bruins L, Demler T, Müller N, Haertle L, Garitano A, Steinbrunn T, Danhof S, Cuenca I, Barrio-Garcia C, Braggio E, Rosenwald A, Martinez-Lopez J, Rasche L, Raab MS, Stewart AK, Einsele Tags: Haematologica Source Type: research

Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura.
Abstract Neurological symptoms related to microthrombosis are the hallmark of acute manifestations of acquired thrombotic thrombocytopenic purpura. Despite the achievement of hematological remission, patients may report persisting neurological impairment that affects their quality of life. To assess the long-term neuropsychological consequences of acute thrombotic thrombocytopenic purpura, we recruited 35 acquired thrombotic thrombocytopenic purpura patients (77% females, median age at onset 41 years, interquartile range 35-48) regularly followed at our out-patient clinic of thrombotic microangiopathies in Milan (...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Riva S, Mancini I, Maino A, Ferrari B, Artoni A, Agosti P, Peyvandi F Tags: Haematologica Source Type: research

Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer.
anga A Abstract In cancer patients, hypercoagulability is a common finding and it has been associated to an increased risk of venous thromboembolisms, but also to tumor proliferation and progression. In this prospective study, in a large cohort of patients with breast cancer, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Giaccherini C, Marchetti M, Masci G, Verzeroli C, Russo L, Celio L, Sarmiento R, Gamba S, Tartari CJ, Diani E, Vignoli A, Malighetti P, Spinelli D, Tondini C, Barni S, Giuliani F, Petrelli F, D'Alessio A, Gasparini G, De Braud F, Santoro A, Labianca R, Fa Tags: Haematologica Source Type: research

Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research.
oss I, Beitinjaneh AM, Muffly L, Vij R, Olsson RF, Byrne M, Schultz KR, Aljurf M, Seftel M, Savoie ML, Savani BN, Verdonck LF, Cairo MS, Hossain N, Bhatt VR, Frangoul HA, Abdel-Azim H, Al Malki M, Munker R, Rizzieri D, Khera N, Nakamura R, Ringdén O, van der Poel M, Murthy HS, Liu H, Mori S, De Oliveira S, Bolaños-Meade J, Elsawy M, Barba P, Nathan S, George B, Pawarode A, Grunwald M, Agrawal V, Wang Y, Assal A, Castillo Caro P, Kuwatsuka Y, Seo S, Ustun C, Politikos I, Lazarus HM, Saber W, Sandmaier BM, de Lima M, Litzow M, Bachanova V, Weisdorf D, Acute Leukemia Committee of the CIBMTR Abstract Cyt...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Lazaryan A, Dolan M, Zhang MJ, Wang HL, Kharfan-Dabaja MA, Marks DI, Bejanyan N, Copelan E, Maijhail N, Waller EK, Chao N, Prestidge T, Nishihori T, Kebriaei P, Inamoto Y, Hamilton B, Hashmi SK, Kamble RT, Bacher U, Hildebrandt GC, Stiff PJ, McGuirk J, Al Tags: Haematologica Source Type: research

Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders.
Abstract Daily intravenous arsenic trioxide administered with all-trans retinoid acid, the standard-of-care for acute promyelocytic leukemia, is costly and challenging to administer. ORH-2014 is a novel, oral arsenic trioxide formulation, consisting of micron-size drug particles with rapid dissolution and high bioavailability. We conducted a multicenter Phase 1 dose-escalating study in patients with advanced hematologic malignancies. Twelve patients received ORH-2014 at 5 mg (n=3), 10 mg (n=6), or 15 mg (n=3) orally once a day (fasted state). Objectives were to assess the safety, tolerability and pharmacokinetics ...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Ravandi F, Koumenis I, Johri A, Tallman M, Roboz GJ, Strickland S, Garcia-Manero G, Borthakur G, Naqvi K, Meyer M, Pudipeddi M, Nidarmarthy S, Vaddi K, Kantarjian H Tags: Haematologica Source Type: research

Transforming activities of the NUP98-KMT2A fusion gene associated with myelodysplasia and acute myeloid leukemia.
Abstract Inv(11)(p15q23) found in myelodysplastic syndromes and acute myeloid leukemia leads to expression of a fusion protein consisting of the N-terminal of nucleoporin 98 (NUP98) and the majority of the lysine methyltransferase 2A (KMT2A) transcript. To explore the transforming potential of this fusion we established inducible iNUP98-KMT2A transgenic mice. After a median latency of 80 weeks, over 90% of induced mice developed signs of disease, including anemia and reduced bone marrow cellularity, increased white blood cell numbers, extramedullary hematopoiesis, and multi-lineage dysplasia. Additionally, inducti...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Fisher JN, Thanasopoulou A, Juge S, Tzankov A, Bagger FO, Mendez MA, Peters AHFM, Schwaller J Tags: Haematologica Source Type: research

D'domain Region Arg782-Cys799 of Von Willebrand Factor contributes to Factor VIII binding.
Abstract In the complex with Von Willebrand Factor, factor VIII (FVIII) is protected from rapid clearance from the circulation. Although it has been established that the FVIII binding site resides in the N-terminal D'-D3 domains of Von Willebrand Factor, detailed information about the amino acid regions that contribute to FVIII binding is still lacking. In the present study, Hydrogen- deuterium exchange mass spectrometry was employed to gain insight into the FVIII binding region on Von Willebrand Factor. To this end, time-dependent deuterium incorporation was assessed in D'-D3 and the FVIII - D'-D3 complex. Data s...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Przeradzka MA, van Galen J, Ebberink EHTM, Hoogendijk AJ, van der Zwaan C, Mertens K, van den Biggelaar M, Meijer AB Tags: Haematologica Source Type: research

SETDB1 mediated histone H3 lysine 9 methylation suppresses MLL-fusion target expression and leukemic transformation.
Abstract Epigenetic regulators play a critical role in normal and malignant hematopoiesis. Deregulation, including epigenetic deregulation, of the HOXA gene cluster drives transformation of about 50% of acute myeloid leukemia. We recently showed that the Histone 3 Lysine 9 methyltransferase SETDB1 negatively regulates the expression of the pro-leukemic genes Hoxa9 and its cofactor Meis1 through deposition of promoter H3K9 trimethylation in MLL-AF9 leukemia cells. Here, we investigated the biological impact of altered SETDB1 expression and changes in H3K9 methylation on acute myeloid leukemia. We demonstrate that S...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Ropa J, Saha N, Hu H, Peterson LF, Talpaz M, Muntean AG Tags: Haematologica Source Type: research

The microRNA miR-196b acts as tumor suppressor in Cdx2 driven acute myeloid leukemia.
L, Buske C Abstract PMID: 31558674 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Rawat VPS, Götze M, Rasalkar A, Vegi NM, Ihme S, Thoene S, Pastore A, Bararia D, Döhner H, Döhner K, Feuring-Buske M, Quintanilla-Fend L, Buske C Tags: Haematologica Source Type: research

Effect of daratumumab on normal plasma cells, polyclonal immunoglobulin levels, and vaccination responses in extensively pre-treated multiple myeloma patients.
Abstract PMID: 31558675 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Frerichs KA, Bosman PWC, van Velzen JF, Fraaij PLA, Koopmans MPG, Rimmelzwaan GF, Nijhof IS, Bloem AC, Mutis T, Zweegman S, van de Donk NWCJ Tags: Haematologica Source Type: research

Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population.
Abstract Fanconi anemia, an inherited bone marrow failure syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with Fanconi anemia from the Israeli inherited bone marrow failure registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 (range 0.1-49) years; sixty-three percent were offspring of consanguineous parents. One-hundred...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Steinberg-Shemer O, Goldberg TA, Yacobovich J, Levin C, Koren A, Revel-Vilk S, Ben-Ami T, Kuperman AA, Shkalim Zemer V, Toren A, Kapelushnik J, Ben-Barak A, Miskin H, Krasnov T, Noy-Lotan S, Dgany O, Tamary H Tags: Haematologica Source Type: research

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.
n P, Zieger B, Cuker A, Devreese K, Tosetto A, De Candia E, Dupuis A, Miyazaki K, Othman M, Gresele P Abstract Major surgery is associated with an increased risk of venous thromboembolism, thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of venous thromboembolism in patients with inherited platelet disorders undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Paciullo F, Bury L, Noris P, Falcinelli E, Melazzini F, Orsini S, Zaninetti C, Abdul-Kadir R, Obeng-Tuudah D, Heller P, Glembotsky AC, Fabris F, Rivera J, Lozano ML, Butta N, Favier R, Cid AR, Fouassier M, Podda GM, Santoro C, Grandone E, Henskens Y, Nurd Tags: Haematologica Source Type: research

Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract.
Abstract Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of 10 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4+ (n=4), CD8+ (n=4), CD4+/CD8+ (n=1) and CD4-/CD8- (n=1)...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Soderquist CR, Patel N, Murty VV, Betman S, Aggarwal N, Young KH, Xerri L, Leeman-Neill R, Lewis SK, Green PH, Hsiao S, Mansukhani MM, Hsi ED, de Leval L, Alobeid B, Bhagat G Tags: Haematologica Source Type: research

The architecture of neoplastic follicles in follicular lymphoma; analysis of the relationship between the tumor and follicular helper T-cells.
Abstract CD4+ T-follicular helper cells are essential for the survival, proliferation, and differentiation of germinal center B-cells and have been implicated in the pathogenesis of follicular lymphoma. To further define the role of these cells in follicular lymphoma, we used multiparameter confocal microscopy to compare the architecture of normal and neoplastic follicles and next generation sequencing to analyze the T-cell receptor repertoire in follicular lymphoma lymph nodes. Multiparameter analysis of lymph nodes showed that the proportion of T-follicular helper cells in normal and neoplastic follicles is the ...
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Townsend W, Pasikowska M, Yallop D, Phillips EH, Patten PEM, Salisbury JR, Marcus R, Pepper A, Devereux S Tags: Haematologica Source Type: research

Genetic platelet depletion is superior in platelet transfusion compared to current models.
Abstract Genetically modified mice advanced our knowledge on platelets in hemostasis and beyond tremendously. However, mouse models harbor certain limitations, including availability of platelet specific transgenic strains, and off-target effects on other cell types. Transfusion of genetically modified platelets into thrombocytopenic mice circumvents these problems. Additionally, ex vivo treatment of platelets prior to transfusion eliminates putative side effects on other cell types. Thrombocytopenia is commonly induced by administration of anti-platelet antibodies, which opsonize platelets to cause rapid clearanc...
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Salzmann M, Schrottmaier WC, Kral-Pointner JB, Mussbacher M, Volz J, Hoesel B, Moser B, Bleichert S, Morava S, Nieswandt B, Schmid JA, Assinger A Tags: Haematologica Source Type: research

Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia.
Abstract Cancer cells undergo massive alterations in their DNA methylation patterns which result in aberrant gene expression and malignant phenotypes. Abnormal DNA methylation is a prognostic marker in several malignancies, but its potential prognostic significance in adult T-cell acute lymphoblastic leukemia is poorly defined. Here, we performed methylated DNA immunoprecipitation to obtain a comprehensive genome-wide analysis of promoter methylation in adult T-cell Acute Lymphoblastic Leukemia (n=24) compared to normal thymi (n=3). We identified a CpG hypermethylator phenotype that distinguishes two T-cell acute ...
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Touzart A, Boissel N, Belhocine M, Smith C, Graux C, Latiri M, Lhermitte L, Mathieu EL, Huguet F, Lamant L, Ferrier P, Ifrah N, Macintyre E, Dombret H, Asnafi V, Spicuglia S Tags: Haematologica Source Type: research

Unique clinico-biological, genetic and prognostic features of adult early T cell precursor acute lymphoblastic leukemia.
ya M, Mercadal S, Artola MT, Cladera A, Tormo M, Bermúdez A, Vall-Llovera F, Martínez P, Amigo ML, Monsalvo S, Novo A, Cervera M, García-Guiñon A, Juncà J, Ciudad J, Orfao A, Ribera JM Abstract PMID: 31537688 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Genescà E, Morgades M, Montesinos P, Barba P, Gil C, Guàrdia R, Moreno MJ, Martínez-Carballeira D, García-Cadenas I, Vives S, Ribera J, González-Campos J, González-Gil C, Zamora L, Ramírez JL, Díaz-Beya M, Mercadal S, Artola MT, Cladera A, Tormo M Tags: Haematologica Source Type: research

KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study.
da Silva M, Santoro A, Molinari A, Ferreri A, Grønbæk K, Piccin A, Cortelazzo S, Bertoni F, Ladetto M, Gaidano G Abstract In recent years, the outcome of mantle cell lymphoma has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of mantle cell lymphoma patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in mantle cell lymphoma, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enroll...
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Ferrero S, Rossi D, Rinaldi A, Bruscaggin A, Spina V, Eskelund CW, Evangelista A, Moia R, Kwee I, Dahl C, Di Rocco A, Stefoni V, Diop F, Favini C, Ghione P, Mahmoud AM, Schipani M, Kolstad A, Barbero D, Novero D, Paulli M, Zamò A, Jerkeman M, Gomez da Si Tags: Haematologica Source Type: research

Disease progression in myeloproliferative neoplasms: comparing patients in accelerated phase with those in chronic phase with Increased blasts ( < 10%) or with other types of disease progression.
Disease progression in myeloproliferative neoplasms: comparing patients in accelerated phase with those in chronic phase with Increased blasts (
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Geyer JT, Margolskee E, Krichevsky SA, Cattaneo D, Boiocchi L, Ronchi P, Lunghi F, Scandura JM, Ponzoni M, Hasserjian RP, Gianelli U, Iurlo A, Orazi A Tags: Haematologica Source Type: research

Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the acute leukemia working party of the EBMT.
omon S, Romee R, Lewalle P, Gayoso J, Maschan M, Lazarus HM, Ballen K, Giebel S, Baron F, Ciceri F, Esteve J, Gorin NC, Spyridonidis A, Schmid C, Ciurea SO, Nagler A, Mohty M Abstract Donor lymphocyte infusion has been used in the management of relapsed disease hematological malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematological relapse, being able to induce durable remissions in a subset of patients. With the increased in the use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of do...
Source: Haematologica - September 19, 2019 Category: Hematology Authors: Dholaria B, Savani BN, Labopin M, Luznik L, Ruggeri A, Mielke S, Al Malki MM, Kongtim P, Fuchs E, Huang XJ, Locatelli F, Aversa F, Castagna L, Bacigalupo A, Martelli M, Blaise D, Ben Soussan P, Arnault Y, Handgretinger R, Roy DC, O'Donnell P, Bashey A, So Tags: Haematologica Source Type: research