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Issue 10, Volume 127

Cover Figure: NF-κB family members RelB and cRel are required for B-cell development. See the article by Almaden et al.

WASHINGTON, March 10, 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.

Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms

Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis

Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants
About 30% of essential thrombocythemia and primary myelofibrosis cases are associated with mutations in the calreticulin gene (CALR). Three papers in this week's issue elucidate the mechanism by which mutant CALR induces myeloproliferation. Using a range of techniques, Araki et al, Marty et al, and Chachoua et al demonstrate that mutant CALR binds to and activates the thrombopoietin receptor. These studies provide important insights into pathogenesis and offer new entry points for therapy of CALR-positive myeloproliferative neoplasms.

Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation
L5 is a strongly electronegative subfraction of low-density lipoproteins that induces platelet activation. In this week's Blood, Shen and colleagues report that both L5 levels and the expression of the L5 receptor LOX-1 are markedly elevated in patients with ischemic stroke and that LOX-1 levels correlate with stroke size. These observations provide an important link between the L5 lipid profile, platelets, and stroke, and they suggest that downregulation of LOX-1 might be uniquely effective in preventing cerebrovascular events.

The immunogenicity of platelet-derived FVIII in hemophilia A mice with or without preexisting anti-FVIII immunity
The development of factor VIII (FVIII) inhibitors is a major impediment to the treatment of hemophilia A. In this issue of Blood, Chen and colleagues demonstrate that infusion of platelets containing FVIII does not trigger primary or memory immune responses in FVIII-null mice, even those with inhibitors. If these observations hold true in humans with hemophilia A, platelet FVIII delivery could provide an important therapeutic modality for patients with inhibitors.

Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation
In this issue, Evans and colleagues report on the role of hypoxia-inducible factor 1 (HIF1) in cancer-associated thrombosis. They report that tissue-specific HIF1α deletion in tumor cells or endothelial cells has divergent impacts on clotting. While deletion from tumor cells decreases cell adhesion, clotting, and fibrin deposition, deletion from endothelial cells increases fibrin deposition. These divergent effects again underscore the complexity of tumor-associated thrombosis and may have important implications for potential therapies manipulating this pathway.

Introduction to a review series: megakaryocytes to platelets in health and disease
In this week's issue, Blood presents a review series on the theme "Megakaryocytes to platelets in health and disease": a collection of articles focused on megakaryocytes and platelets and their potential development as in vitro resources for transfusion and for drug delivery. The reviews focus on the latest developments in ex vivo production of platelets and place these developments in the context of normal and abnormal megakaryocyte development and platelet production.

The articles in this review series, Megakaryocytes to platelets in health and disease, include the following:

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.

blood® is a registered trademark of the American Society of Hematology.