MLL: a histone methyltransferase disrupted in leukemia.
Rearrangements of the MLL gene, which is located at chromosome 11q23, are associated with aggressive acute leukemias in both children and adults. MLL regulates Hox gene expression through direct promoter binding and histone modification. MLL rearrangements occurring in leukemia include MLL fusion genes, partial tandem duplications of MLL and MLL amplification. MLL fusions and amplification upregulate Hox expression, apparently resulting in a block of hematopoietic differentiation. Future therapies for MLL-associated leukemia might involve blocking Hox gene upregulation by using fusion proteins or inhibiting the activity of Hox proteins themselves.
Hess
Jay L
JL
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 413b Stellar Chance Laboratories, Philadelphia, PA 19104, USA. jhess@mail.med.upenn.edu
D004268:DNA-Binding Proteins / Q000235:genetics*; D005784:Gene Amplification; D020440:Gene Duplication; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008957:Models, Genetic; D051788:Myeloid-Lymphoid Leukemia Protein; D011496:Protein Methyltransferases; D011519:Proto-Oncogenes / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase