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Issue 24, Volume 127

Cover Figure: Identification of a myeloid-specific CEBPA enhancer region. See the article by Avellino et al.

WASHINGTON, June 16, 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.

Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients
Claushuis and colleagues report on the influence of admission thrombocytopenia on the outcome of over 900 consecutive patients with sepsis from two hospital ICUs. Admission thrombocytopenia was independently associated with enhanced mortality and disturbed host response biomarkers.

IL-4 enhances expression and function of surface IgM in CLL cells
B-cell receptor (BCR) inhibitors are effective agents with increasing use in the treatment of chronic lymphocytic leukemia (CLL). Aguilar-Hernandez and colleagues demonstrate that interleukin-4 (IL-4), secreted by T cells in CLL, can decrease the effect of BCR inhibition through increasing expression of surface immunoglobulin M (IgM) on CLL cells. These studies suggest that targeting IL-4 through inhibition of downstream JAK3/STAT6 signaling with JAK inhibitors might enhance the effectiveness of BCR inhibitors.

Men with severe hemophilia in the United States: birth cohort analysis of a large national database
Mazepa and colleagues report on prospective data gathered by the Centers for Disease Control and Prevention (CDC) on 4899 men with severe hemophilia. Analyzed by birth cohorts, the data document improvements in access to care, frequency of prophylaxis, and decreased disability. However, frequent bleeding persists in more than one-third of patients, and liver failure remains the leading cause of death.

Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura
In a Letter to Blood, Page and colleagues present an analysis of the Oklahoma registry to assess the impact of rituximab on thrombotic thrombocytopenic purpura relapse. Despite patient heterogeneity and a retrospective approach, results suggest that rituximab markedly reduces relapse risk.

Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group
In a Perspective, Sonneveld and colleagues present a consensus update of a cytogenetics-based definition for high-risk multiple myeloma. They use cytogenetic abnormalities to revise the definition of high-risk myeloma in the International Staging System and assess the impact of available treatment modalities on outcomes.

An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation

Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors

CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML
C/EBPαis a transcription factor expressed in a tissue-specific manner in several tissues. It is required for neutrophil differentiation and is frequently mutated in AML. Three reports in this issue are focused on C/EBP in normal and acute myeloid leukemia (AML) myeloid cells.

In the first, Avellino and colleagues present a series of elegant functional genomic studies that delineate the requirements for neutrophil-specific C/EBP gene expression. Among 14 identified potential enhancer regions, they identify a single +42-kb enhancer required for the myeloid lineage and demonstrate that deletion of this region in mice leads to severe defects in neutrophil differentiation without affecting any other C/EBPα-expressing tissues.

In another article (Lavallée et al) and a Letter to Blood (Maxson et al), deep sequencing of samples from adult and pediatric patients with AML reveals that patients with mutations in C/EBPα have increased JAK2 signaling and an unexpected increase in mutations in the G-CSF receptor. AML blasts from this subset respond in vitro to JAK2 inhibitors, suggesting that this may allow targeted therapy for this subset of AML patients.

 

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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