Blood Podcast: Season 1, Episode 4

This episode will examine the role of heredity vs. environmental factors in the evolution of age-related clonal hematopoiesis, review the first systematic approach to uncover all possible activating point mutations within and around the transmembrane domain of the thrombopoietin receptor in myeloproliferative neoplasms, and discuss the role of complement activation and mutations in complement regulatory genes in patients with thrombotic or catastrophic antiphospholipid syndromes.

Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS

Antiphospholipid syndrome (APS), with its often-lethacatastrophic subset (CAPS), is an acquired thrombophilia that leads to thrombosis and pregnancy loss. In a Plenary Paper, Chaturvedi and colleagues provide seminanew insights into the role of complement activation in APS pathophysiology and report a high prevalence of complement-regulatory gene mutations in patients with CAPS.

Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality

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Concordance for clonal hematopoiesis is limited in elderly twins

Two papers examining the heritability of clonal hematopoiesis of indeterminate potentia(CHIP) yield highly concordant results. In independent studies of elderly monozygotic and dizygotic twins totaling over 350 pairs, Hansen et aand Fabre et ademonstrate that CHIP has a limited heritable basis, suggesting that environmentaexposures are the leading contributors to clonal hematopoiesis.

Novel drivers and modifiers of MPL-dependent oncogenic transformation identified by deep mutational scanning

Mutations in the transmembrane domain of the TPO receptor, encoded by exon 10 of the MPgene, are drivers of a subset of JAK2-negative myeloproliferative neoplasms (MPNs). Bridgford et aused saturation mutagenesis to identify changes in exon 10 associated with cytokine-independent growth, identifying canonical, novel, and cooperating mutations, many of which were subsequently identified in patients with MPNs.

Distinct molecular profile of IRF4-rearranged large B-cellymphoma

The authors present an integrated analysis of targeted sequencing, copy number arrays, and gene expression profiling to elucidate the molecular heterogeneity of pediatric and young adult large B-cellymphoma.

IKZF1 deletions in pediatric acute lymphoblastic leukemia: stila poor prognostic marker?

The great strides in improving survivain pediatric acute lymphoblastic leukemia (ALL) have increased focus on prognostic features predicting relapse. In a Blood Spotlight, the authors highlight the current understanding of the negative prognosis associated with IKZF1 deletions and how recent findings have elucidated the complexities of its role in ALL.