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Volume 1, Issue 14

 

Cover Image

Cover Figure: Phagocytosis of anti-RhD–opsonized red blood cells by human splenocytes
See the article by Meinderts et al.

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WASHINGTON, June 13,  2017 – Welcome to the “Advance Notice,”  newsletter which provides highlights from issues of Blood Advances, the open-access journal of the American Society of Hematology (ASH), that  are hand-picked by Blood Advances Editor-in-Chief Robert Negrin, MD.

The field of anticoagulants has changed dramatically in recent years, providing many therapeutic options for treatment of patients with thrombotic events and for prevention of thrombosis in high-risk patient populations. In a Blood Advances Talk,  Mark Crowther discusses these new agents and compares them with the age-old drug warfarin. We hope you enjoy listening to this talk and hearing about the many new agents that are available.

The differentiation of hematopoietic stem cells (HSCs) and progenitor cells is of critical importance in health and disease. This complex process is not well understood. Yu et al performed a genome-wide chromatin analysis of long-term HSCs, short-term HSCs and multipotent progenitors using an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). This interesting manuscript enhances our understanding of this process and will serve as a reference for future discovery.

There has been much interest in cellular populations capable of suppressing immune responses and the plasticity of these immune effector cells. The study by Ribechini et al provides important insights into the role of cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in signaling through the IFNgR/IRF1 and AKT/mTOR pathways. Cytokine GM-CSF signaling results in licensing of monocytes with immunosuppressive function. These observations deepen our understanding of the role of monocytes in regulating immune responses under certain conditions.

The use of induced pluripotent stem cells (iPSCs) is an exciting model system to study complex and often difficult-to-study diseases. In the study by Pittermann et al, the congenital neutropenic disorder Kostmann disease associated with the homozygous HAX1W44X nonsense mutation was evaluated. Targeted correction of this mutation was achieved by using the CRISPR-Cas9 system, rescuing neutrophil differentiation and correcting this genetic defect. This approach holds great promise for studying and developing treatments for this disorder and many others.

Blood is a precious resource provided by generous donors. To assess adequate hemoglobin before blood donation, a standard approach is the measurement of capillary hemoglobin. In this study by Niittymäki et al of the Finnish Red Cross Blood Service, the time needed for hemoglobin recovery in more than 1.1 million donors was assessed over a 5-year period. The authors found interesting recovery times, including a subset of donors who can donate frequently. This important study highlights critical blood donor parameters to optimize this critical resource.

The clearance of opsonized red blood cells (RBCs) is thought to primarily occur in the spleen by macrophages. The article by Meinderts et al challenges that conclusion and demonstrates a role for neutrophils and monocytes in addition to macrophages. Further, a role for CD47 engagement is identified in this process. These findings broaden our understanding of RBC clearance and are important as therapeutics targeting CD47 are developed.

Red blood cells are an essential resource required for a number of medical interventions and procedures. Therefore, maintaining an adequate supply of red cell products is of critical importance. In this issue, Greinacher et al explore the impact of demographic changes on the donation of blood products and their use. Understanding these relationships can ensure an adequate supply of this precious resource.

Patients with myeloproliferative neoplasms often have a JAK2 V617F mutation. When this mutation arises is a matter of debate. McKerrell and colleagues followed 12 patients with JAK2 mutant MPNs who had donated blood 4.5 to 15 years prior. Their findings are provocative.

 

In an Exceptional Case Report, Attarian and colleagues discuss a challenging case of a patient with acute intermittent porphyria and renal failure, which commonly occurs in these patients. They evaluate the effects of hemin therapy and hemodialysis on porphobilinogen and 5-aminolevulinic acid levels.

Featured Visual Abstract

Microenvironmental agonists drive de novo phenotypic resistance to ibrutinib plus venetoclax in MCL and CLL

Kallesh D. Jayappa, Craig A. Portell, Vicki L. Gordon, Brian J. Capaldo, Stefan Bekiranov, Mark J. Axelrod, L. Kyle Brett, Julia D. Wulfkuhle, Rosa I. Gallagher, Emanuel F. Petricoin, Timothy P. Bender, Michael E. Williams and Michael J. Weber

 

 

 

 

Blood Advances is the official open-access 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.