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. email@example.comShow MeSH
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Mentions: One may envision different scenarios underlying the divergent fates of BCR/ABLp185+ and BCR/ABLp210+ LT-HSCs: First, the transformed LT-HSCs may constantly self-renew and supply the leukaemic cell pool in the periphery. Alternatively, the transformed LT-HSCs may represent a pre-leukaemic stage and self-renewal occurs after differentiation into a more mature stage (see scheme in Fig 2A). Thus, we analysed the abundance of GFP+ LT-HSCs in BM from moribund mice originally transplanted with either BCR/ABLp185- or BCR/ABLp210-infected LT-HSCs. We hardly detected GFP+ cells within the HSC-subpopulations in BCR/ABLp185-transplanted mice (Fig 2B, and Supporting Information Fig S2A and B, n = 3). In contrast, GFP+ cells were readily detectable in all HSC-subpopulations of BCR/ABLp210-transplanted mice (69.1 ± 5.7% GFP+ cells within LT-HSCs, Fig 2B; 78.4 ± 8.4% in ST-HSCs and 29 ± 12.3% in MPPs, Supporting Information Fig S2A). The total numbers of HSCs were ∼20 fold increased (Supporting Information Fig S2B, n = 3). Notably, we also detected few BCR/ABLp185+ cells within the CLMP population, (Fig 2C). In contrast, the vast majority of BCR/ABLp210+ CLMPs were GFP+ (Fig 2C). Taken together, these data suggest that mature CML is continuously supplied by the COCs, whereas the initial B-ALL COC-population is lost in case of B-ALL.
Affiliation: Research Institute of Molecular Pathology (I.M.P.), Vienna, Austria. firstname.lastname@example.org