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Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes
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Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes
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Journal Article
Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes
2022
Overview
High levels of the inflammatory cytokine IL-6 in the bone marrow are associated with poor outcomes in pediatric acute myeloid leukemia (pAML), but its etiology remains unknown. Using RNA-seq data from pre-treatment bone marrows of 1489 children with pAML, we show that > 20% of patients have concurrent IL-6, IL-1, IFNα/β, and TNFα signaling activity and poorer outcomes. Targeted sequencing of pre-treatment bone marrow samples from affected patients (
n
= 181) revealed 5 highly recurrent patterns of somatic mutation. Using differential expression analyses of the most common genomic subtypes (~60% of total), we identify high expression of multiple potential drivers of inflammation-related treatment resistance. Regardless of genomic subtype, we show that JAK1/2 inhibition reduces receptor-mediated inflammatory signaling by leukemic cells in-vitro. The large number of high-risk pAML genomic subtypes presents an obstacle to the development of mutation-specific therapies. Our findings suggest that therapies targeting inflammatory signaling may be effective across multiple genomic subtypes of pAML.
IL6 expression in the bone marrow is associated with reduced survival in paediatric AML. Here, the authors used RNA-seq to identify treatment resistance-associated co-occurring inflammatory signalling in leukemic cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
