Diverging fates of cells of origin in acute and chronic leukaemia.
Bottom Line: During disease-maintenance, CML LT-HSCs persist to function as cancer stem cells (CSCs) that maintain leukaemia and require signalling by the transcription factor STAT5.In contrast, B-ALL LT-HSCs differentiate into CSCs that correspond to pro-B cells.This transition step requires a transient IL-7 signal and is lost in IL-7Rα-deficient cells.
Affiliation: Research Institute of Molecular Pathology (I.M.P.), Vienna, Austria. firstname.lastname@example.orgShow MeSH
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Mentions: In contrast to the CSC model, the stochastic model does not discriminate between pseudo-hierarchical tumours (Quintana et al, 2010) and non-hierarchical tumours (Williams et al, 2007). Hence, we devised three hypothetical scenarios how BCR/ABLp210 CML and BCR/ABLp185 B-ALL progress based on the phenotypical characterization and hierarchical structure of the haematopoietic system (Fig 5A). In the first model, all leukaemic cells are capable to maintain leukaemia irrespective of their phenotype. The second model assumes that only one subtype of phenotypically defined cells act as a CSC. In the third model, rare HSC-like cells exclusively function as CSCs.
Affiliation: Research Institute of Molecular Pathology (I.M.P.), Vienna, Austria. email@example.com