Review
Nature Reviews Cancer 7, 823-833 (November 2007) | doi:10.1038/nrc2253
MLL translocations, histone modifications and leukaemia stem-cell development
Andrei V. Krivtsov1 & Scott A. Armstrong1 About the authors
Abstract
Translocations 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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Author affiliations
- Division of Haematology/Oncology, Children's Hospital, Department of Pediatric Oncology, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence to: Scott A. Armstrong1 Email: Scott.Armstrong@childrens.harvard.edu
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