Open AccessDiverging fates of cells of origin in acute and chronic leukaemia
Author(s) -
Kovacic Boris,
Hoelbl Andrea,
Litos Gabriele,
Alacakaptan Memetcan,
Schuster Christian,
Fischhuber Katrin M.,
Kerenyi Marc A.,
Stengl Gabriele,
Moriggl Richard,
Sexl Veronika,
Beug Hartmut
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100208
Subject(s) - haematopoiesis , stem cell , biology , stat5 , cancer stem cell , cancer research , phenotype , breakpoint cluster region , immunology , myeloid , microbiology and biotechnology , genetics , signal transduction , receptor , gene
The large difference in phenotypes among tumour populations may stem from the stochastic origin of tumours from distinct cells – tumour cells are assumed to retain the phenotypes of the cells from which they derive. Yet, functional studies addressing the cellular origin of leukaemia are lacking. Here we show that the cells of origin of both, BCR/ABL‐induced chronic myeloid (CML) and B‐cell acute lymphoid leukaemia (B‐ALL), resemble long‐term haematopoietic stem cells (LT‐HSCs). 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. Thus, in BCR/ABLp185 + B‐ALL and BCR/ABLp210 + CML, the final phenotype of the tumour as well as the abundance of CSCs is dictated by diverging differentiation fates of their common cells of origin.