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Volume 129, Issue 13

Cover Figure: Novel mechanism of coagulopathy in APL. See the article by Verhoef et al.

WASHINGTON, March 30, 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.

Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma
Gayle et al provide evidence that apilimod, a potent and selective PIKfyve inhibitor, induces significant cytotoxicity at clinically achievable concentrations in preclinical models of B-cell non-Hodgkin lymphoma via inhibition of the autophagy flux and perturbation of lysosome homeostasis.

Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism
Riedl et al examine the link between tumor podoplanin expression in brain tumors and the prothrombotic state inherent to glioma. They show that podoplanin expression is associated with altered coagulation activation and an increased risk of venous thromboembolism.

Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs
This study uses CD99 knockout mice to explore the contributions of endothelial CD99 to neutrophil extravasation during inflammation and furnishes novel insights into the role of CD99 in neutrophil adhesion to the endothelium.

Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production and ameliorates anemia of chronic disease in rodents
Asshof and colleagues demonstrate how the JAK2 inhibitor momelotinib, used in the treatment of myelofibrosis, ameliorates anemia in a rat model of chronic inflammation. Momelotinib inhibits ALK2, the tyrosine kinase downstream of the receptor for bone morphogenic proteins, and stimulates hepcidin production.

Lymphangiogenesis is a feature of acute GVHD, and VEGFR-3 inhibition protects against experimental GVHD
This paper reports a role for lymphangiogenesis in graft-versus-host disease (GVHD) and postulates inhibition of angiogenesis by targeting VEGFR3 as a potential new therapy for GVHD.

Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era

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Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia
In the all-trans-retinoic acid (ATRA) treatment era, life-threatening hemorrhage has remained the major cause of death in acute promyelocytic leukemia (APL). In their study, Mantha et al advance our understanding of clinical risk factors of hemorrhagic death. In a second study, Cao et al report data that reveal a novel mechanism of coagulopathy in APL that is induced by treatment with ATRA.

Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel
Under the auspices of the European LeukemiaNet, the authors offer a consensus guide regarding the use of allogeneic hematopoietic cell transplantation in adults with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML).

Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells
Kunimoto et al examine the role of Aid (activation-induced cytidine deaminase) in hematopoietic stem cells (HSC) and myeloid/erythroid differentiation and define the hematopoietic phenotype of Aid deficiency. Aid deficiency promotes anemia and myeloid expansion, but it does not alter HSC function nor enhance leukemogenesis.

 

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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