Issues

Inflammation is a hallmark of cancer known in myeloid malignancies to dysregulate the function and differentiation trajectories of hematopoietic stem and progenitor cells (HSPC), contributing to disease progression. However, individual cell populations comprising the complex inflammatory signaling networks in human acute myeloid leukemia (AML) have not been fully mapped out. As the cover illustrates, Chen et al. compose an atlas of normal human bone marrow at single-cell resolution, identifying diverse populations of HSPC niche-supporting bone marrow stromal cells (BMSC) and HSPCs. Similar charting of the AML bone marrow niche uncovered expansion of proinflammatory BMSCs concurrent with specific depletion of high-output HSPCs, leading to altered hematopoiesis. As highlighted by Lisi-Vega and Méndez-Ferrer’s In the Spotlight on p. 349, the inflammatory cell types and gene expression signatures associated with this remodeling unexpectedly correlated with reduced risk for relapse and better outcomes in AML patients, suggesting that relapse-initiating leukemic cells are dependent on BMSC signaling depleted by inflammatory microenvironment remodeling. For details, see the article on p. 394. Cover image by Tetiana Vavryk.