MLL translocations, histone modifications and leukaemia stem-cell development.
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.
Krivtsov
Andrei V
AV
Division of Haematology/Oncology, Children's Hospital, Department of Pediatric Oncology, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Armstrong
Scott A
SA
D000328:Adult; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002843:Chromatin / Q000648:ultrastructure; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000235:genetics*; D008745:Methylation; D051379:Mice; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000166:cytology; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D011496:Protein Methyltransferases; D011499:Protein Processing, Post-Translational
D002843:Chromatin; D006657:Histones; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse