MLL translocations, histone modifications and leukaemia stem-cell development.
review · Level V
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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.
Medical subject headings
- Epigenesis, Genetic
- Gene Expression Regulation
- Histone-Lysine N-Methyltransferase
- Histones
- Leukemia
- Myeloid-Lymphoid Leukemia Protein