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Sung K Chiu, Stephanie L Orive, Mitchell J Moon, Jesslyn Saw, Sarah Ellis, Ben T Kile, Yizhou Huang, Diego Chacon, John E Pimanda, Dominik Beck, Justin R Hamilton, Cedric S Tremblay, David J Curtis
The Stem Cell Leukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for normal megakaryopoiesis. However, unlike other members of this complex such as Gata1, Fli1 and Runx1, mutations of Scl have not been observed as a cause of inherited thrombocytopenia. We postulated that functional redundancy with its closely related family member, Lymphoblastic Leukemia 1 (Lyl1) might explain this observation. To determine if Lyl1 can substitute for Scl in megakaryopoiesis, we examined the platelet phenotype of mice lacking one or both factors in megakaryocytes...
July 12, 2019: Blood
Ciara L Freeman, Robert Kridel, Alden A Moccia, Kerry J Savage, Diego R Villa, David W Scott, Alina S Gerrie, David Ferguson, Fergus Cafferty, Graham W Slack, Pedro Farinha, Brian Skinnider, Joseph M Connors, Laurie H Sehn
Despite widespread use of bendamustine and rituximab (BR) as frontline therapy for advanced stage follicular lymphoma (FL), little is known about the risk of early progression or incidence of histological transformation. We performed a retrospective analysis of a population-based cohort of 296 patients with advanced stage FL treated with frontline BR and maintenance rituximab. As previously demonstrated, outcomes with this regimen are excellent, with 2-year EFS estimated at 85% [95% CI 80-89%] and 2-year OS 92% (95% CI 88-95%)...
July 12, 2019: Blood
Deya Cherpokova, Charlotte Camille Jouvene, Stephania Libreros, Elise DeRoo, Long Chu, Xavier de la Rosa, Paul Norris, Denisa D Wagner, Charles N Serhan
Deep vein thrombosis (DVT) is a common cardiovascular disease with a major impact on quality of life, and safe and effective therapeutic measures to efficiently reduce existent thrombus burden are scarce. Using a comprehensive targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)‑based metabololipidomics approach, we established temporal clusters of endogenously biosynthesized specialized pro-resolving mediators (SPMs) and proinflammatory and prothrombotic lipid mediators during DVT progression in mice...
July 12, 2019: Blood
Blood Journal Staff
The Editors of Blood retract the 24 February 2011 paper cited above. Concerns regarding the data underlying Figures 3A, 3B, 3C, 4A, and 5C were brought to the attention of Stanford University. The university investigated the issue, conducting a search for any original sources of these data. The search was unsuccessful; the experiments, data, and figure preparation for these figures were overseen by Holbrook E. Kohrt, who passed away before the university became aware of the concerns. As a result, the data underlying these figures cannot be validated...
July 11, 2019: Blood
Stefano Luminari, Michele Merli, Sara Rattotti, Vittoria Tarantino, Luigi Marcheselli, Federica Cavallo, Marzia Varettoni, Benedetta Bianchi, Francesco Merli, Alessandra Tedeschi, Giuseppina Cabras, Francesca Re, Carlo Visco, Marcia Torresan Delamain, Emanuele Cencini, Michele Spina, Simone Ferrero, Angela Ferrari, Marina Deodato, Donato Mannina, Ombretta Annibali, Angela Rago, Lorella Orsucci, Irene Defrancesco, Marco Frigeni, Marina Cesaretti, Luca Arcaini
Marginal zone Lymphomas (MZL) are indolent B cell non Hodgkin Lymphoma (INFL) and have a heterogeneous clinical behavior. Recently time to progression shorter than 24 months (POD24) was identified to stratify overall survival (OS) in follicular NHL and in INFL. Here we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry (NCT02904577) headed by Fondazione Italiana Linfomi (FIL). POD24 was calculated only for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis...
July 10, 2019: Blood
Jason Dehn, Stephen Spellman, Carolyn K Hurley, Bronwen E Shaw, Juliet N Barker, Linda J Burns, Dennis L Confer, Mary Eapen, Marcelo Anibal Fernandez-Vina, Robert Hartzman, Martin Maiers, Susana R Marino, Carlheinz Mueller, Miguel-Angel Perales, Raja Rajalingam, Joseph Pidala
Allogeneic hematopoietic cell transplantation involves consideration of both donor and recipient characteristics to guide the selection of a suitable graft. Sufficient high resolution donor-recipient human leukocyte antigen (HLA) match is of primary importance in transplantation with adult unrelated donors, using conventional graft-versus-host disease prophylaxis. In cord blood transplantation, optimal unit selection requires consideration of unit quality, cell dose and HLA-match. In this summary, the National Marrow Donor Program® (NMDP) and the Center for International Blood and Marrow Transplant Research® (CIBMTR), jointly with the NMDP Histocompatibility Advisory Group, provide evidence-based guidelines for optimal selection of unrelated donors and cord blood units...
July 10, 2019: Blood
Alison Wakoff Loren, Suneeta Senapati
Patients with hematologic malignancies and those undergoing hematopoietic cell transplantation (HCT) face a complex set of challenges when considering options for fertility preservation (FP). There are no standard options for pre-pubertal children, and women with hematologic malignancies may not be eligible for standard FP options. Fortunately, initial therapies for most blood cancers are not highly gonadotoxic, affording an important opportunity for post-remission counseling and referrals to fertility specialists...
July 10, 2019: Blood
Anja Mottok, Stacy S Hung, Elizabeth A Chavez, Bruce Woolcock, Adèle Telenius, Lauren C Chong, Barbara Meissner, Hisae Nakamura, Christopher Rushton, Elena Viganò, Clementine Sarkozy, Randy D Gascoyne, Joseph M Connors, Susana Ben Neriah, Andrew Mungall, Marco A Marra, Reiner Siebert, David W Scott, Kerry J Savage, Christian Steidl
Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking...
July 10, 2019: Blood
Philipp B Staber, Marco Herling, Mar Bellido, Eric D Jacobsen, Matthew S Davids, Tapan Mahendra Kadia, Andrei Shustov, Olivier Tournilhac, Emmanuel Bachy, Francesco Zaja, Kimmo Porkka, Gregor Hoermann, Ingrid Simonitsch, Claudia Haferlach, Stefan Kubicek, Marius Mayerhoefer, Georg Hopfinger, Ulrich Jaeger, Claire Dearden
T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of T-PLL patients it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG)set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL and will thus support clinical decision making as well as the approval of new therapeutics by healthcare authorities...
July 10, 2019: Blood
Brian Giacopelli, Qiuhong Zhao, Amy S Ruppert, Akwasi Agyeman, Christoph Weigel, Yue-Zhong Wu, Madelyn M Gerber, Kari G Rabe, Melissa C Larson, Junyan Lu, James S Blachly, Kerry A Rogers, William G Wierda, Jennifer R Brown, Kanti R Rai, Michael Keating, Laura Z Rassenti, Thomas J Kipps, Thorsten Zenz, Tait D Shanafelt, Neil E Kay, Lynne V Abruzzo, Kevin R Coombes, Jennifer A Woyach, John C Byrd, Christopher C Oakes
Alterations in global DNA methylation patterns are a major hallmark of cancer and represent attractive biomarkers for personalized risk stratification. Chronic lymphocytic leukemia (CLL) risk stratification studies typically focus on time to first treatment (TTFT), time to progression (TTP) after treatment, and overall survival (OS). Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies such as the Bruton's tyrosine kinase inhibitor, ibrutinib...
July 10, 2019: Blood
Antonio R Lucena-Araujo, Juan L Coelho-Silva, Diego A Pereira-Martins, Douglas R Silveira, Luisa Corrêa de Araujo Koury, Raul A M Melo, Rosane Bittencourt, Katia Pagnano, Ricardo Pasquini, Elenaide C Nunes, Evandro M Fagundes, Ana B Gloria, Fabio R Kerbauy, Maria de Lourdes Chauffaille, Israel Bendit, Vanderson Rocha, Armand Keating, Martin S Tallman, Raul C Ribeiro, Richard Dillon, Arnold Ganser, Bob Löwenberg, Peter Valk, Francesco Lo Coco, Miguel A Sanz, Nancy Berliner, Eduardo M Rego
Combining the analysis of mutations with aberrant expression of genes previously related to poorer prognosis in both acute promyelocytic leukemia (APL) and acute myeloid leukemia, we propose an integrative score in APL (ISAPL) and demonstrate its relationship with clinical outcomes of patients treated with all-trans retinoic acid (ATRA) in combination with anthracycline-based chemotherapy. Based on FLT3 -ITD mutational status, ΔNp73/TAp73 expression ratio, ID1 , BAALC , ERG , and KMT2E gene expression levels, we modeled ISAPL in 159 patients (median ISAPL score: 3, range: 0-10)...
July 10, 2019: Blood
Wei Jian Tan, Mona Meng Wang, Paola Ricciardi-Castagnoli, Tiffany Tang, Soon Phaik Chee, Tong Seng Lim, Anita Sook Yee Chan
No abstract text is available yet for this article.
July 10, 2019: Blood
Takaaki Maekawa, Shoichiro Kato, Toshikuni Kawamura, Kohei Takada, Takehiro Sone, Hiraku Ogata, Keita Saito, Takuya Izumi, Shigeki Nagao, Kosuke Takano, Yosuke Okada, Noriaki Tachi, Masahiro Teramoto, Toshikatsu Horiuchi, Reina Hikota-Saga, Kaori Endo-Umeda, Shigeyuki Uno, Yukiko Osawa, Ayako Kobayashi, Shinichi Kobayashi, Ken Sato, Michihiro Hashimoto, Shinya Suzu, Kensuke Usuki, Soji Morishita, Marito Araki, Makoto Makishima, Norio Komatsu, Fumihiko Kimura
Monocyte-derived fibrocytes recently garnered attention as the novel pathogenesis of myelofibrosis (MF) and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule-F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in PB of HCs, myeloproliferative neoplasm (MPN) patients without MF, and MPN patients with MF using a cross-sectional approach...
July 3, 2019: Blood
Tianyuan Hu, Kiyomi Morita, Matthew C Hill, Yajian Jiang, Ayumi Kitano, Yusuke Saito, Feng Wang, Xizeng Mao, Kevin A Hoegenauer, Kazuhiro Morishita, James F Martin, P Andrew Futreal, Koichi Takahashi, Daisuke Nakada
Oncogenic mutations confer cells the ability to propagate indefinitely, but whether oncogenes alter the cell fate of these cells is unknown. Here, we show that the transcriptional regulator PRDM16s causes oncogenic fate conversion by transforming cells fated to form platelets and erythrocytes into myeloid leukemia stem cells (LSCs). Prdm16s expression in megakaryocyte-erythroid progenitors (MEPs), which normally lack the potential to generate granulo-monocytic cells, caused AML by converting MEPs to LSCs. Prdm16s blocked megakaryocytic/erythroid potential by interacting with super enhancers and activating myeloid master regulators, including PU...
July 3, 2019: Blood
Saad Z Usmani, Hareth Nahi, Maria-Victoria Mateos, Niels W C J van de Donk, Ajai Chari, Jonathan L Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Peter Hellemans, Tara Masterson, Pamela L Clemens, Man Luo, Kevin Liu, Jesus San Miguel
Daratumumab, a human monoclonal antibody targeting CD38, is approved as monotherapy and in combination regimens for patients with multiple myeloma (MM). Currently, daratumumab is administered IV. The phase 1b PAVO (MMY1004) study evaluated subcutaneously administered daratumumab in combination with the recombinant human hyaluronidase PH20 enzyme (rHuPH20) in patients with relapsed or refractory MM (RRMM). Part 1 of the study, reported here, evaluated a mix-and-deliver (MD) formulation of daratumumab and rHuPH20 (DARA-MD) administered by subcutaneous infusion...
July 3, 2019: Blood
Giorgia Battipaglia, Myriam Labopin, Nicolaus Kröger, Antonin Vitek, Boris Afanasyev, Inken Hilgendorf, Johannes Schetelig, Arnold Ganser, Didier Blaise, Maija Itälä-Remes, Jakob R Passweg, Francesca Bonifazi, Jurgen Finke, Annalisa Ruggeri, Arnon Nagler, Mohamad Mohty
The use of antithymocyte globulin (ATG) has represented the standard of care in graft-versus-host (GVHD) prophylaxis in patients undergoing mismatched unrelated donor (MMUD) transplant. The safety and feasibility of post-transplant cyclophosphamide (PTCY) in this setting has recently been reported, but no studies have compared to date the outcomes of PTCY versus ATG in a 9/10 MMUD transplant. Using the registry data of the ALWP of the EBMT we performed a matched-pair analysis comparing those two strategies in a 9/10 MMUD setting...
July 3, 2019: Blood
Craig S Sauter, Brigitte Senechal, Isabelle Rivière, Ai Ni, Yvette Bernal, Xiuyan Wang, Terence Purdon, Malloury Hall, Ashvin N Singh, Victoria Z Szenes, Sarah Yoo, Ahmet Dogan, Yongzeng Wang, Craig H Moskowitz, Sergio Giralt, Matthew J Matasar, Miguel-Angel Perales, Kevin J Curran, Jae Park, Michel Sadelain, Renier J Brentjens
High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or chemorefractory diffuse large B-cell lymphoma (rel/ref DLBCL). Only 50% of patients are cured with this approach. We investigated whether CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT may enhance progression-free survival (PFS). METHODS: Eligibility for this study includes poor-risk rel/ref aggressive B-NHL chemosensitive to salvage therapy with: 1) FDG-PET (+) or 2) bone marrow involvement...
July 1, 2019: Blood
Jue Wang, Usha R Pendurthi, L Vijaya Mohan Rao
Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of the coagulation. Typically, most of TF on cell surfaces exist in a cryptic, coagulant inactive state, but transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology...
July 1, 2019: Blood
Aaron C Petrey, Dana R Obery, Sean P Kessler, Ash Zawerton, Bruno Flamion, Carol A de la Motte
Platelets are specialized cells essential for hemostasis that also function as crucial effectors capable of mediating inflammatory and immune responses. These sentinels continually survey their environment and discriminate between homeostatic and danger signals, such as modified components of the extracellular matrix (ECM). The glycosaminoglycan hyaluronan (HA) is a major ECM component coating the vascular lumen and under normal conditions restricts access of inflammatory cells. In response to tissue damage, the endothelial HA matrix enhances leukocyte recruitment and regulates the early stages of the inflammatory response...
July 1, 2019: Blood
Anna Holthenrich, Hannes C A Drexler, Tarek Chehab, Johannes Naß, Volker Gerke
Weibel-Palade bodies (WPB) are unique secretory organelles of endothelial cells that store factors regulating vascular haemostasis and local inflammation. Endothelial activation triggers rapid exocytosis of WPB, leading to the surface presentation of adhesion molecules relevant for leukocyte rolling (P-selectin) and platelet capture (von-Willebrand factor, VWF). Despite its role as an important secretory organelle, a comprehensive compilation of factors associated with WPB has not been carried out. We addressed this by a proximity proteomics approach employing the peroxidase APEX2 coupled to two known WPB-associated proteins, the Rab GTPases Rab3b and Rab27a...
July 1, 2019: Blood
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