Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo

Journal article

Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which differentcancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function invivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs invivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation. © 2014 Elsevier Inc.

Authors: Woll, P; Kjällquist, U; Chowdhury, O; Doolittle, H; Wedge, D

• Publisher: Cell Press
• Journal: Cancer Cell
• Volume: 25
• Issue: 6
• Pages: 794-808
• Publication date: 2014-06-16
• DOI: 10.1016/j.ccr.2014.03.036
• EISSN: 1878-3686
• ISSN: 1535-6108
• Language: English