(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email email@example.com.
Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy, Jodele et al.
While hematopoietic stem cell transplant-associated thrombotic microangiopathy is recognized as a common post-transplant complication, it remains poorly understood. The hallmark of all thrombotic microangiopathies is vascular endothelial cell injury of various origins, resulting in microangiopathic hemolytic anemia, platelet consumption, fibrin deposition in the microcirculation, and tissue damage. In this week’s issue of Blood, investigatorsreport results of an analysis of the complement alternative pathway, identifying deletions in complement Factor H (CFH)-related genes 3 and 1 and/or anti-CFH antibodies in six children who developed a post-transplant thrombotic microangiopathy. The data indicate that complement alternative pathway dysregulation appears to be involved in the pathogenesis of post-transplant thrombotic microangiopathy. These intriguing findings shed light on a novel mechanism of endothelial injury in transplant-associated thrombotic microangiopathy and may guide the development of targeted treatment.
Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura, Deford et al.
Patients who have suffered acute episodes of thrombotic thrombocytopenic purpura (TTP) typically recover completely, however they may experience minor cognitive abnormalities and carry a risk of relapse. A manuscript in this week’s issue of Blood provides important new data on the long-term outcomes of TTP survivors, reporting that patients recovering from a TTP episode carry an increased long-term risk of hypertension, major depression, and premature death. These original, novel data suggest that TTP shares many features of chronic diseases and should be considered as such.
Specific gene delivery to liver sinusoidal and artery endothelial cells, Abel et al.
Endothelial cells (EC) fulfill distinct tasks depending on their microenvironment; however, they are difficult to genetically manipulate in vivo for functional studies or gene therapy. Results from a manuscript published in this week’s issue of Blood validate a new paradigm for highly specific lentiviral targeting into these endothelial cells in vivo that may help overcome previous barriers to achieving efficient and specific in vivo targeting of sinusoidal endothelial cells (LSEC) and arterial endothelial cells. In the manuscript the authors use erythropoietin to demonstrate its potential therapeutic utility in elevating hematocrit levels and observe that delivery of the erythropoietin gene results in substantially increased erythropoietin and hematocrit levels. This strategy offers novel options to better understand the physiological functions of endothelial cells and to treat genetic diseases such as those affecting blood factors.
Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells, Li et al.
Translocations in the mixed-lineage leukemia gene MLL1 encode fusion proteins retaining the N-terminus of MLL1, which interacts with the tumor suppressor menin. This interaction is essential for leukemogenesis and offers a promising drug target in mixed-lineage leukemias. However, wild-type MLL1 plays a critical role in sustaining hematopoietic stem cells and disruption of an essential MLL1 co-factor might block normal hematopoiesis. The significance of the work published in this issue of Blood revolves around the conclusion that menin is not a critical co-factor for MLL1 in normal hematopoiesis. In the manuscript, investigators demonstrate that the disruption of oncogenic MLL1-menin interaction does not impact the functions of normal MLL1 and menin in blood cells undergoing normal hematopoiesis or in B-cell differentiation. Presenting data from experiments using cells from various mouse models of MEN1 and MLL1 gene deletion, Li and colleagues add direct positive support to the development of menin-MLL1 disrupting drugs as selective leukemia-targeting agents.
Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration, Aoyama et al.
Graft-versus-host disease (GVHD) is a critical complication of allogeneic stem cell transplantation. During GVHD, donor T cells are activated by host antigen-presenting cells and differentiate into T effector cells that migrate to GVHD target organs. However, local environmental factors influencing T effector cell differentiation and migration are largely unknown. In this week’s issue of Blood, investigators report results from an examination of the role of retinoic acid, which is produced by vitamin A metabolism in the intestine and contributes to intestinal homeostatis and tolerance induction, in the development of GVHD. In the manuscript the authors demonstrate that blocking retinoic acid receptor signaling in donor T cells reduces interferon gamma production and homing of T cells into the intestinal tract. Importantly, this action reduces GVHD while graft-versus-leukemia effects are maintained.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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