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Issue 2, Volume 128

Cover Figure: Interferon-α signaling promotes embryonic HSC maturation. See the article by
Kim et al
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WASHINGTON, July 14,  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.

Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by defective Fas signaling and lymphocyte accumulation that has been attributed to failure of apoptosis. Völkl and colleagues demonstrate that lymphoproliferation in ALPS is a more active process, with active proliferation and aberrant T-cell maturation induced by mammalian target of rapamycin (mTOR) signaling. This suggests that rapamycin might be uniquely suited for treatment of the disorder.

Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera
Hepcidin is the master regulator of iron metabolism, acting by decreasing iron absorption from the gastrointestinal tract and release of iron from macrophages. Abnormally low hepcidin in the face of iron overload contributes to the pathophysiology of β-thalassemia intermedia, and iron availability controls the erythroid hyperproliferation in polycythemia vera (PV). Casu and colleagues report that administration of minihepcidin improves iron overload in murine β-thalassemia and decreases splenomegaly and polycythemia in a mouse model of PV. These exciting results promise to have a major impact on therapy for iron-overload syndromes and polycythemia.

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells
von Willebrand factor (VWF) is present in 2 pools, 1 in the circulation and 1 in the subendothelium. Lopes da Silva and Cutler characterize the carefully regulated pathways governing secretion to those 2 sites. High-molecular-weight VWF is secreted from Weibel-Palade bodies from the apical side of the endothelial cells, where it interacts with platelets and clotting factors to promote thrombus formation. Lower-molecular-weight VWF is secreted from the basal surface, where it provides a subendothelial pool that protects from endothelial injury.

Prophylactic efficacy of BeneFIX vs Alprolix in hemophilia B mice

FVIII-binding IgG modulates FVIII half-life in patients with severe and moderate hemophilia A without inhibitors
These 2 papers provide important insights into the clinical effects of recombinant factor replacement therapy in hemophilia.

In the first, Cooley and colleagues examine the physiologic efficacy of short vs long-acting factor IX (FIX) in a murine model of hemophilia B. The physiologic effect of FIX is strongly influenced by extravascular FIX bound to collagen IV. Here, the authors demonstrate that although circulating levels of FIX were higher 1 week after infusion of Alprolix (FIXFc) than after BeneFIX (FIXwt), protection from bleeding was identical, supporting the importance of the peripheral collagen IV-bound stores of FIX and challenging the clinical superiority of long-acting FIX.

In the second, Hofbauer and colleagues examine the variable pharmacokinetics of FVIII in patients with hemophilia A. They demonstrate that some patients without inhibitors harbor low-titer FVIII-binding IgG that decreases the half-life of FVIII. Assay for these antibodies may help to optimize prophylactic regimens for hemophilia A patients.

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma
Assouline and colleagues report a phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma that demonstrates responses in 28% of patients. Importantly, genomic studies and assay of circulating tumor DNA enriched the data by demonstrating features that predict subsets of patients with higher and lower rates of response.

 

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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