Kawano Y, Kawano H, Ghoneim D, Fountaine TJ, Byun DK, LaMere MW, Mendler JH, Ho TC, Salama NA, Myers JR, Hussein SE, Frisch BJ, Ashton JM, Azadniv M, Liesveld JL, Kfoury Y, Scadden DT, Becker MW, Calvi LM. 2023. Myelodysplastic syndromes disable human CD271+VCAM1+CD146+ niches supporting normal hematopoietic stem/progenitor cells. bioRxiv : the preprint server for biology. Pubmed: 37066307 DOI:10.1101/2023.04.09.536176


Mesenchymal stem/stromal cells (MSCs) within the bone marrow microenvironment (BMME) support normal hematopoietic stem and progenitor cells (HSPCs). However, the heterogeneity of human MSCs has limited the understanding of their contribution to clonal dynamics and evolution to myelodysplastic syndromes (MDS). We combined three MSC cell surface markers, CD271, VCAM-1 (Vascular Cell Adhesion Molecule-1) and CD146, to isolate distinct subsets of human MSCs from bone marrow aspirates of healthy controls (Control BM). Based on transcriptional and functional analysis, CD271+CD106+CD146+ (NGFR+/VCAM1+/MCAM+/Lin-; NVML) cells display stem cell characteristics, are compatible with murine BM-derived Leptin receptor positive MSCs and provide superior support for normal HSPCs. MSC subsets from 17 patients with MDS demonstrated shared transcriptional changes in spite of mutational heterogeneity in the MDS clones, with loss of preferential support of normal HSPCs by MDS-derived NVML cells. Our data provide a new approach to dissect microenvironment-dependent mechanisms regulating clonal dynamics and progression of MDS.

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David Scadden’s laboratory is dedicated to discovering the principles governing blood cell production, with the ultimate goal of guiding the development of therapies for blood disorders and cancer.

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