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Volume 130, Issue 14

Cover Figure: NOX2-derived superoxide drives mitochondrial transfer from marrow stromal cells to AML blasts. See the article by Marlein et al.

WASHINGTON, October 5, 2017 – 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.

NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts
Acute myeloid leukemia (AML) blasts depend on oxidative phosphorylation to generate ATP, and they have more mitochondria than normal stem cells. In a series of elegant studies, Marlein and colleagues demonstrate that AML blasts acquire increased mitochondria from bone marrow stromal cells via transfer through nanotubes. The process is dependent on NADPH oxidase-2 (NOX2)–generated superoxide, and inhibition of NOX2 blocks transfer and is toxic to leukemic cells.

Selective factor VIII activation by the tissue factor–factor VIIa–factor Xa complex
The current view of coagulation posits that tissue factor (TF) initiates a cascade of events that generates thrombin, with subsequent amplification of coagulation reflecting thrombin-induced activation of factors V and VIII. Kamikubo and colleagues delineate a novel function of TF by which TF directly activates factor VIII independent of thrombin, promoting early coagulation prior to amplification.

HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies
The efficacy of anti-CD20 antibodies is limited by downregulation of surface CD20 expression by tumor cells; pan-HDAC inhibitors upregulate CD20 but at the cost of significant toxicity. Bobrowicz et al demonstrate in preclinical studies that HDAC6-specific inhibition upregulates CD20, supporting clinical trials of combined HDAC6 inhibitors and anti-CD20 antibodies.

Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations
Hairy cell leukemia (HCL) is characterized by frequent mutations in BRAF and MAP2K1, but cooperating mutations remain to be fully characterized. Durham and colleagues present results of deep sequencing to identify novel cooperating mutations governing disease heterogeneity and resistance to chemotherapy in HCL.

Integrin αIIbβ3outside-in signaling
Durrant et al provide an extensive review of platelet signaling from integrin αIIbβ3 (glycoprotein IIb-IIIa), a critical player in multiple platelet processes.

Pregnancy outcomes in inherited bone marrow failure syndromes

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Pregnancies in patients with inherited bone marrow failure syndromes in the NCI cohorts
Two Letters to Blood in this issue review the outcomes of pregnancy in patients with inherited bone marrow failure (IBMF). Gansner et al report that infertility and pregnancy loss are common in patients with IBMF, although successful births can occur, and Giri et al corroborate these findings in their patients. Both groups advocate multidisciplinary management of these complicated pregnancies.

 

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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