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Volume 129, Issue 16

Cover Figure: PAK4 as a potential therapeutic target in multiple myeloma. See the article
by Fulciniti et al.

WASHINGTON, April 20, 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.

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma
Noy and colleagues present results of a phase 2 trial of ibrutinib for patients with relapsed/refractory marginal zone lymphoma, demonstrating durable responses in approximately half of the patients.

Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma
Fulciniti et al report preclinical studies confirming that p21-activated kinase 4 (PAK4) is highly expressed in myeloma and that a PAK4 inhibitor is cytotoxic to myeloma cells in culture and in mouse xenografts.

Anti-CD20-interleukin-21 fusokine targets malignant B cells via direct apoptosis and NK-cell–dependent cytotoxicity
Bhatt and colleagues present preclinical data on a novel molecule fusing anti-CD20 to interleukin-21, demonstrating increased efficacy against lymphoma cells in comparison with either agent alone.

Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms
Ataxia-pancytopenia syndrome is an autosomal dominant disorder characterized by neurologic disorders, cytopenias, and predisposition to myeloid leukemia involving −7/del(7q). Tesi and colleagues identify novel heterozygous gain-of-function mutations in SAMD9L, located on chromosome 7q, that suppress hematopoiesis and progress to myelodysplastic syndrome (MDS) in a setting of allelic loss.

Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke
The major complication of thrombolysis with tissue plasminogen activator (tPA) in the setting of stroke is hemorrhagic conversion. Using a mouse model, Simão and colleagues demonstrate that hemorrhagic complications are mediated by tPA-induced upregulation of plasma kallikrein, inhibition of which increases the effectiveness of tPA and reduces hemorrhagic complications.

Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development
Subramaniam et al elucidate the growing understanding of the links between hemostasis and complement factors, and they demonstrate that C3 enhances platelet activation and C5 increases clot stability through interaction with myeloid cells.

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines
In this month’s CME article, van Nimwegen and colleagues present a nested case-control study of heart failure risk in Hodgkin lymphoma survivors. They demonstrate a dose-related risk associated with radiation that increases nearly 3-fold with the use of anthracycline chemotherapy.

The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality
Hill et al use quantitative polymerase chain reaction to detect multiple double-stranded DNA viruses in plasma after allogeneic hematopoietic cell transplantation (HCT). They show that the cumulative burden of these viruses is predictive of mortality.

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study
HCT may be curative of hematologic complications of Fanconi anemia (FA), but radiation may increase the risk of later solid tumors. Mehta and colleagues report excellent success in a multi-institutional study of a radiation-free preparative regimen for alternative-donor HCT for FA.

 

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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