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Issue 9, Volume 128

Cover Figure: Identification of a clinically relevant population of Tregs in aplastic anemia. See the article by Kordasti et al.

WASHINGTON, September 1, 2016 – 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.

Deep phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment
In this issue of Blood, Kordasti et al identify a distinct population of regulatory T cells (Tregs) with greater immunoregulatory properties that associate with disease onset and response to immunosuppressive therapy in aplastic anemia (AA). This adds entirely novel insight into our understanding of the altered immune system in AA.

Identification of factors promoting ex vivo maintenance of mouse hematopoietic stem cells by long-term single-cell quantification
Kokkaliaris et al employ a novel sophisticated single-cell time-lapse imaging approach to track the behavior of individual murine hematopoietic stem cells (HSCs) cultured on stromal cells. They demonstrate the profound effect of cell contact to stroma on the survival of HSCs cultured in vitro and identify a novel stem cell survival molecule, dermatopontin, thereby laying the groundwork for the in vitro manipulation of HSCs for therapeutic purposes.

Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes
This paper reports a high incidence of mutations in CRBN (cereblon) and RAS pathway genes in multiple myeloma, in particular highly frequent mutations in KRAS/NRAS and BRAF (72%) and a relatively high frequency of TP53 mutations, as well as various novel mutations in CRBN, CUL4B, IKZF1, and IRF4.

Carfilzomib significantly improves the progression free survival of high-risk patients in multiple myeloma
Avet-Loiseau et al report results of a detailed unique cytogenetic analysis of a randomized phase 3 trial comparing carfilzomib, lenalidomide, and dexamethasone to lenalidomide and dexamethasone in patients with relapsed myeloma. The results have direct clinical significance for the treatment of relapsed myeloma.

Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas
This paper reports a comprehensive landscape of structural gene rearrangements of the programmed death ligand (PDL) locus (9p24.1) harboring PDL1/CD274 and PDL2/PDCD1LG2, thus providing critical information about the breakpoint anatomy of these rearrangements in B-cell lymphoma.

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma
By using an integrative approach of mate-pair DNA and RNA next-generation sequencing, Boddicker et al furnish important information about chromosomal rearrangements in peripheral T-cell lymphoma, identifying novel fusions involving VAV1 and other targetable fusion genes.

Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure
In this week’s Blood, Mossner et al take important next steps in understanding the genomic evolution of myelodysplastic syndromes (MDS). Their studies offer novel insights into the clonal evolution of MDS during natural progression of the disease and characterize preexisting minor clones that survive treatment.

Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction
Lozano et al describe 3 patients from 2 unrelated families who have severe inherited platelet dysfunction and bleeding diathesis, displaying two novel homozygous mutations in RAS guanyl-releasing protein 2 (RASGRP2), the gene encoding calcium- and DAG-regulated guanine exchange factor 1 (CalDAG-GEFI). These data show the critical importance of integrin-regulating molecules in platelet function.

Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation
In a review article, Welsh et al summarize the current understanding of the role of platelets in lymphovenous hemostasis and lymphatic vessel maturation, and they discuss the implications of defective lymphovenous hemostasis for human disease.

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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