Volume 131, Issue 21



May 24, 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: Review series: emerging biological insights into lymphoid tumors. See the articles in this review series.

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphomay
This report presents studies exploring inhibition of signaling across key nodes in the B-cell receptor (BCR) signaling pathway for Bruton tyrosine kinase (BTK)–sensitive and BTK-insensitive diffuse large B-cell lymphoma.

A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
The authors generated an impressive resource of single-cell transcriptomic data from murine bone marrow–derived hematopoietic stem and progenitor cells. They profiled approximately 45,000 wild-type cells and 13,000 V831M c-Kit mutant (W41/W41) mouse bone marrow using single-cell RNA sequencing, and they provide a novel comprehensive transcriptional landscape that identifies 8 different blood lineage fates.

Patients with CD3G mutations reveal a role for human CD3γ in Treg diversity and suppressive function
The authors of this paper focus on the key problem of autoimmunity in relation to CD3γ deficiency and offer a plausible and testable hypothesis (abnormal Treg and Tconv repertoires). They verified the hypothesis experimentally in a rigorous manner with multiple patients. These original data on CD3γ− regulatory cells furnish an explanation for the predisposition to autoimmunity in CD3γ deficiency.

NADPH oxidase activation regulates apoptotic neutrophil clearance by murine macrophages
It is still a mystery why patients with chronic granulomatous disease (CGD) have autoimmune and autoinflammatory symptoms. In a compelling study, the investigators provide data to explain the molecular basis for the exuberant inflammation seen in patients with CGD, demonstrating that these patients cannot handle apoptotic neutrophils properly because their macrophages lack the capacity to sufficiently degrade these apoptotic cells.

Introduction to a review series on biological insights into lymphoid tumors
This series of four reviews on biologic insights into lymphoid tumors highlights recent insights into a range of lymphoid tumors in an era of explosively increasing knowledge of genetics, epigenetics, and tumor-environment interactions and clinical testing of precision drug targeting.

The articles in this review series, "Biological insights into lymphoid tumors", include the following:

Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study
This clinical report by Ahn et al of a study in which the majority of patients with chronic lymphocytic leukemia (CLL) were treatment naïve presents a 5-year follow-up on efficacy and toxicity of single-agent ibrutinib, an inhibitor of BCR-associated BTK. This study complements another recent 5-year follow-up study of (mostly) relapsed/refractory patients [O’Brien et al, Blood. 2018;131(17):1910-1919].

Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1
This study adds to the broad general concept that blood clotting proteases possess remarkable biologic activities independent of their influence on coagulation. It presents the discovery that coagulation factor VIIa exerts physiologically relevant protective effects in endothelial cells and whole-organism inflammatory responses by initiating cell signaling that is anti-inflammatory via at least two receptors, endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR1).

Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up
Kreitman and colleagues update the high response rate in a study of moxetumomab pasudotox in patients with relapsed hairy cell leukemia. They demonstrate the value of minimal residual disease (MRD) assessment with flow cytometry. Patients who became MRD negative had significant longer duration of complete remission.


View this week's complete table of contents

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