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Volume 1, Issue 7

 

Cover Image

Cover Figure: Snapshot at 230 ns from molecular dynamics simulations of a representative structure of αIIbβ3 headpiece-fibrinogen γ-module complex showing a relaxed model of fibrinogen γ-module binding to αIIbβ3.
See the article by Zafar et al.

Join the discussion @ Blood Advances Community Conversations

WASHINGTON, February 28,  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.

In a Blood Advances Talk, Roberts discusses the exciting development and clinical application of the BCL2 inhibitor venetoclax. This oral agent has resulted in impressive response rates in patients with relapsed chronic lymphocytic leukemia and mantle cell lymphoma, but clearly this is the tip of the iceberg as new combinations are sure to be tested. We hope you enjoy listening to this primer on this exciting new agent.

Carfilzomib is a new and effective agent for the treatment of multiple myeloma. However, it has been associated with cardiac and renal dysfunction. Dimopoulos et al detail these toxicities in a cohort of 60 patients, highlighting that toxicities to these organs are reasonably common and should be considered in patients undergoing treatment with this drug.

Much progress has been made in the treatment of patients with multiple myeloma (MM). Despite this progress, MM remains an incurable disease. With the increasing number of active agents, the choice of which drugs to utilize is a challenging one. In the network meta-analysis by Botta et al, different regimens are analyzed for use in relapsed and refractory patients. Their results are interesting, informative, and may help guide therapy in this challenging clinical setting.

Induced pluripotent stem cells hold promise in a variety of different settings, including the production of blood cells. In the report by Aihara and colleagues, a novel c-MPL agonist, TA-316, significantly enhances the production of platelets from iPS-derived megakaryocyte progenitor cell lines. Sometime in the future this approach could be utilized for platelet production for clinical use.

Platelet integrin receptor aIIbβ3 plays a critical role in platelet aggregation. In the paper by Zafar et al, binding sites in addition to the known fibrinogen C-terminal γ-chain peptide are investigated. They present the interesting hypothesis that conformation changes after platelet activation result in the new ancillary sites that support higher affinity fibrinogen binding interactions and clot retraction.

A major advance in the field of hematopoietic cell transplantation is the availability of alternative donors for patients who do not have a matched sibling. In the manuscript by Versluis et al, on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, a large number of acute myeloid leukemia patients in first complete remission with poor risk features were evaluated based upon donor type. These retrospective data supported the use of matched-related and matched-unrelated donors, but also showed that studies with haploidentical donors are resulting in similar outcomes. Clearly, only prospective randomized clinical trials can answer this question definitively, but it is heartening that results with alternative donors continue to improve, giving more options for patients.

Featured Visual Abstract

Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells

Sarah L. King, Hiren J. Joshi, Katrine T. Schjoldager, Adnan Halim, Thomas D. Madsen, Morten H. Dziegiel, Anders Woetmann, Sergey Y. Vakhrushev, Hans H. Wandall

 

 

 

 

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.