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Issue 18, Volume 127

Cover Figure: Critical role for donor B-cell–secreted antibodies in murine cGVHD. See the article by Jin et al.

WASHINGTON, May 5, 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.

Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials
Böll and colleagues report the outcome of GHSG randomized trials of early-stage Hodgkin disease treatment in patients >60 years of age. They compared 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), 2 cycles of AVD, and 4 cycles of ABVD followed by involved-field radiation in all groups. They report that 2 cycles of ABVD is no more toxic than AVD but that 4 cycles of ABVD is associated with considerable bleomycin toxicity.

The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR
Zhou and colleagues report elegant preclinical studies demonstrating that combining two novel agents resulted in synergy and synthetic lethality in acute myeloid leukemia (AML) cell lines, primary AML cells, and AML xenografts. These effects appeared especially potent in AML with unfavorable genotypes. Further experiments elucidated mechanisms of synergy resulting from combined disruption of the proteasome system and of histone deacetylation. These studies support investigation of this combination in future clinical studies.

Antibodies from donor B cells perpetuate cutaneous chronic graft-versus-host disease in mice
Chronic graft-versus-host disease (cGVHD) is associated with sclerodermatous skin changes that are known to depend on both donor T cells and B cells, but the role of B cells is not understood. Using a murine model, Jin and colleagues demonstrate the central role of donor B-cell-derived antibodies in all aspects of cGVHD. Transplantation with a graft giving rise to B cells with normal antigen presentation and regulatory function but absent antibody secretion blocked damage to the thymus and peripheral organs as well as cutaneous Th17 cell infiltration.

Disturbed B-lymphocyte selection in autoimmune lymphoproliferative syndrome
Autoimmune lymphoproliferative syndrome (ALPS) usually arises as a result of heterozygous mutations in Fas pathway genes, most commonly the Fas receptor gene, but the role of Fas in the B-cell abnormalities and autoimmunity is unknown. Janda and colleagues examined the B cells in a patient with somatic FAS mutation and another patient with a germ line FAS mutation and partial loss of heterozygosity, thereby allowing comparison of B cells with no expression, reduced expression, and normal expression of Fas. Their results suggest that Fas is a gatekeeper that governs B-cell selection and deletion of autoreactive or genomically defective cells.

EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications
The EBF-PDGFRB fusion is found in <1% of B-ALL cases and is seen within the Philadelphia-like ALL subset. Schwab and colleagues review the clinical features of 15 EBF-PDGFRB-positive patients culled from United Kingdom ALL trials. The majority of these patients are minimal residual disease positive at the end of therapy and are refractory to most chemotherapy but respond to imatinib.

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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