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Volume 131, Issue 6

 

 

February 8, 2018 – 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.

Cover Figure: Mutant Srsf2 impairs hematopoietic stem cell function in mice.  See the article by Kon et al.

The interaction of ENL with PAF1 mitigates polycomb silencing and facilitates murine leukemogenesis
ENL, a chromatin reader, is a fusion partner of MLL in leukemia. Hetzner et al dissect the transforming function of ENL and demonstrate that ENL interacts with polymerase-associated factor 1 (PAF1) and overcomes polycomb-related repression to increase gene transcription.


Myosin IIa is critical for cAMP-mediated endothelial secretion of von Willebrand factor
Li and colleagues dissect the mechanism by which von Willebrand factor is secreted from endothelial Weibel-Palade bodies (WPBs). They demonstrate that myosin IIa is required for trafficking of mature WPBs to the cell membrane and exocytosis.


 

Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice
Srsf2 mutation is one of the common splicing factor mutations in myelodysplastic syndromes (MDS). Kon et al demonstrate that conditional knock-in of mutant Srsf2 reduces hematopoietic stem and progenitor cells. In addition, while mice did not spontaneously develop MDS, transplant of the mutant Srsf2 stem cells into irradiated recipients induced MDS, suggesting a role for replicative stress in the progression to an MDS phenotype.


CD38-bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B-cell malignancies
Green and colleagues report preclinical testing of a novel pretargeted radioimmunotherapy strategy based on a CD38-bispecific fusion protein. They demonstrate remarkable efficacy of the agent in mouse xenografts of multiple myeloma and B-cell non-Hodgkin lymphoma.


Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage
Mutations in the calreticulin gene (CALR) are detected in 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis. Li et al studied conditional knockin mice with the mutant CALR under control of the endogenous murine locus; these mice recapitulate the ET phenotype, but their stem cells have no competitive transplantation advantage.


Apoptosis in megakaryocytes and platelets: the life and death of a lineage
In a Blood Spotlight, McArthur and colleagues review the role of BCL-2 family prosurvival proteins in supporting megakaryocyte development and platelet production, as well as the ways in which proapoptotic pathways promote megakaryocyte clearance and limit platelet life span.

 

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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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