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Issue 6, Volume 127

Cover Figure: Macrophage scavenger receptor AI (SR-AI) modulates factor X levels. See the article by Muczynski et al.

WASHINGTON, February 11, 2016 – 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, PhD, and Deputy Editor Nancy Berliner, MD.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes
Human platelet alloantigens caused by single nucleotide polymorphisms are important targets of alloimmune bleeding disorders such as fetal or neonatal thrombocytopenia and posttransfusion purpura. These syndromes are often associated with severe bleeding. In this week's plenary paper, Zhang and colleagues use the CRISPR/Cas9 gene editing system to alter induced pluripotent stem cells to express these rare antigens, providing a novel tool for diagnosis and investigation of alloimmune thrombocytopenias, with the long-term goal of informing therapeutic strategies to improve outcomes.

Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients
Resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) is usually mediated by mutations in the BCR-ABL1 kinase domain. The third-generation TKI ponatinib has activity against most resistance-inducing mutations, including T315I; however, resistance still occurs. In this week's issue, Deininger and colleagues use next-generation sequencing to demonstrate that ponatinib response is not affected by mutation status and resistance is not mediated by acquisition of new mutations; this suggests that ponatinib resistance is mediated by BCR-ABL-independent pathways.

CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia
Immune thrombocytopenia (ITP) is caused by both antibody- and T-cell-mediated immune destruction of platelets. Responses of ITP to rituximab do not seem to be restricted to suppressing antibody-mediated responses, since responding patients may have persistent antibodies and patients without antibodies may respond. In this week's Blood, Guo and colleagues demonstrate in a murine model that B-cell depletion decreases CD8+ T-cell proliferation, increases Tregs, and blocks the development of ITP. This confirmation of the effect of B-cell depletion on T-cell responses has important therapeutic implications for ITP and other autoimmune diseases.

KIT D816V-mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression
In this issue, Garcia-Montero and colleagues report that 25-30% of patients with systemic mastocytosis (SM) have mesenchymal stem cells (MSCs) that carry the somatic KIT D816V mutation. They postulate that SM in these patients arises in a pluripotent progenitor cell that can give rise to both MSCs and hematopoietic cells. These observations provide a potential new paradigm of hematopoiesis and new insights into the clinical features of SM.

Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis
In this week's issue, Aghourian and colleagues report that Gas6 promotes cancer-induced thrombosis through regulation of endothelial expression of prostaglandin E synthase. This leads to increased PGE2 secretion, activating platelets and promoting venous thrombosis. This novel signaling pathway between cancer cells and the endothelium provides new insights into cancer pathophysiology and offers new potential targets for therapeutic intervention.

Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion
About 25-30% of patients with non-del(5q) myelodysplastic syndrome achieve an erythroid response to lenalidomide. In this week's issue, Chesnais and colleagues correlate clinical responses with the clonal architecture before and after lenalidomide. They demonstrate that lenalidomide transiently modulates clonal abnormalities without lasting impact on dominant clones, especially those associated with mutations in SF3B1, TET2, DNMT3A, and ASXL1.

This week's complete table of contents

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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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