Volume 132, Issue 3



July 19, 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: Relevant mouse models of human pathogenetic hypomorphic RAG mutations.
See the article by Ott de Bruin.

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 inhibitor itacitinib in relapsed/refractory B-cell lymphoma
Phosphatidylinositol 3-kinases (PI3Ks) play a pivotal role in low-grade and aggressive B-cell malignancies, but the therapeutic use of PI3K inhibitors has been limited by their associated toxicities. This report presents an interesting approach in which a JAK1 inhibitor, itacitinib, is combined in a phase 1 study with a novel PI3Kδ inhibitor, INCB040093, which may increase efficacy and reduce toxicity.

Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system
The investigators furnish evidence revealing the genetic variation underlying the last unresolved blood group system, XG. They identify a GATA1 single-nucleotide polymorphism (SNP) 3709 bp upstream from the erythroid transcription start site of the XG coding region that explains the relationship between the GATA1 SNP and the Xg(a+) and Xg(a−) phenotypes.

Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells
Metformin induces fetal hemoglobin in a FOXO3-dependent manner in primary human erythroid cells, a mechanism that is different from other inducers, including hydroxyurea. This novel finding may have a significant clinical implication for the treatment of sickle cell disease.

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia
This study demonstrates the superiority of acute lymphoblastic leukemia–type therapy for ambiguous-lineage acute lymphoblastic leukemia in childhood.

Allogeneic hematopoietic stem cell transplantation for T-cell lymphomas
This review examines the role of allogeneic stem cell transplantation for mature T-cell and natural killer cell lymphomas.

How I Treat Burkitt lymphoma in children, adolescents, and young adults in sub-Saharan Africa
In How I Treat article, the authors offer their treatment approach for Burkitt lymphoma, an aggressive yet curable malignancy, in resource-poor settings.

Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response
The authors developed a novel reagent that targets the HSP90 C-terminal domain and inhibits its function. They report that targeting HSP90 dimerization suppresses imatinib-resistant chronic myeloid leukemia (CML) without inducing a heat shock response.

Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A
This study reveals the highly variable involvement of mature hematopoietic lineages with the common clonal mutations in individuals with clonal hematopoiesis of indeterminate potential (CHIP).

Benefit of brentuximab over bleomycin in first-line treatment of advanced-stage Hodgkin lymphoma has not been proven
This Letter to Blood raises some important criticisms and concerns about a study, recently published in the New England Journal of Medicine, that demonstrated a benefit of brentuximab over bleomycin in the first-line treatment of advanced-stage Hodgkin lymphoma.

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