Issue 6, Volume 128

Cover Figure: Dimethyl fumarate inhibits CTCL growth through targeting NF-κB. See the article by Nicolay et al.

WASHINGTON, August 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.

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB
A curative therapy for cutaneous T-cell lymphoma (CTCL) remains elusive. NF-κB is overexpressed in CTCL and is an attractive target for therapy. Nicolay and colleagues demonstrate that dimethyl fumarate (DMF), an approved drug for psoriasis and multiple sclerosis, inhibits growth of CTCL cell lines and primary cells from patients in vitro and in mouse xenograft models in vivo; further, they show that this is linked to NF-κB inhibition. DMF offers promise for the treatment of CTCL.

Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenström macroglobulinemia
Recent studies have confirmed that somatic mutations in MYD88, CXCR4, and ARID1A are highly prevalent in Waldenström macroglobulinemia. Hunter and colleagues correlate the transcriptional profiles associated with these mutations and identify distinct expression signatures associated with MYD88 with and without CXCR4 mutation. These studies promise to lead to more targeted therapies for the disease.

Thrombopoietin receptor agonists shift the balance of Fcγ receptors towards inhibitory receptor IIb on monocytes in ITP
Immune thrombocytopenia (ITP) is associated with an altered immune response, with alterations in Fcγ receptor expression that increase phagocytosis. Liu and colleagues report that the thrombopoietin receptor agonists (TPO-RAs) eltrombopag and romiplostim shift this balance back toward normal, decreasing monocyte phagocytosis. These results help to explain why a subset of TPO-RA–treated patients with ITP show sustained responses after stopping TPO-RA treatment.

Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies
Primary immunodeficiency linked to RAG1 mutations is clinically heterogeneous. Brauer and colleagues use induced pluripotent stem cells to dissect the differences in T-cell development that result from different mutations in RAG1.

The role of leukocytes in thrombosis
There is increasing recognition that leukocytes play an important role in hemostasis through the release of proinflammatory and procoagulant factors that increase thrombogenicity and through modulation of fibrinolysis. Swystun and Liaw review the role of leukocytes in modulating thrombosis and discuss how leukocytes may be a novel target for antithrombotic therapy.

JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis
Patients with JAK2-V617F–negative polycythemia vera often have isolated erythrocytosis and have mutations in JAK2 exon 12. Grisouard and colleagues model JAK2 exon 12–mutant polycythemia vera in mice and demonstrate that they also have isolated erythrocytosis. The authors further demonstrate changes in iron metabolism that support erythroid proliferation.

This week's complete table of contents

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Blood (, 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) (, the world’s largest professional society concerned with the causes and treatment of blood disorders.

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