Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9

Andrei V. Krivtsov, David Twomey, Zhaohui Feng, Matthew C. Stubbs, Yingzi Wang, Joerg Faber, Jason E. Levine, Jing Wang, William C. Hahn, D. Gary Gilliland, Todd R. Golub and Scott A. Armstrong ()
Additional contact information
Andrei V. Krivtsov: Children's Hospital
David Twomey: Children's Hospital
Zhaohui Feng: Department of Pediatric Oncology
Matthew C. Stubbs: Children's Hospital
Yingzi Wang: Children's Hospital
Joerg Faber: Children's Hospital
Jason E. Levine: Children's Hospital
Jing Wang: Department of Pediatric Oncology
William C. Hahn: Medical Oncology, Dana Farber Cancer Institute
D. Gary Gilliland: Brigham and Women's Hospital, Harvard Medical School
Todd R. Golub: Department of Pediatric Oncology
Scott A. Armstrong: Children's Hospital

Nature, 2006, vol. 442, issue 7104, 818-822

Abstract: Identity of cancer stem cells Cancer is thought to arise either from normal tissue cells or committed progenitors. A key question is how in the latter case cancer stem cells with the ability to self-renew — a property lacking in progenitor cells — can arise. A population of mouse leukaemia stem cells capable of initiating leukaemia when as few as four cells are injected into recipient mice has now been isolated from mice in which leukaemia arises through a mutation in committed progenitor cells. This made it possible to use gene expression profiling to determine global cellular identity and to view the transition from normal progenitor to leukaemia stem cell. Remarkably, the leukaemia stem cell largely maintains the gene expression profile of a committed progenitor, while activating a subset of genes normally expressed in haematopoietic stem cells. At least some of these genes are important for self-renewal in the leukaemic stem cells. The differences between leukaemic and normal blood stem cells may also be good news for the prospects of developing a drug that selectively targets cancer stem cells.

Date: 2006
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DOI: 10.1038/nature04980

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