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Nature reviews. Cancer · Nov 2007
ReviewMLL translocations, histone modifications and leukaemia stem-cell development.
- Andrei V Krivtsov and Scott A Armstrong.
- Division of Haematology/Oncology, Children's Hospital, Department of Pediatric Oncology, and Harvard Medical School, Boston, Massachusetts 02115, USA.
- Nat. Rev. Cancer. 2007 Nov 1;7(11):823-33.
AbstractTranslocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis. The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4), and positively regulates gene expression including multiple Hox genes. Leukaemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform haematopoietic cells into leukaemia stem cells. The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development.
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