title: Mixed-Lineage Leukemia Fusions and Chromatin in Leukemia.
abstract: Recent studies have shown the importance of chromatin-modifying complexes in the maintenance of developmental gene expression and human disease. The mixed lineage leukemia gene (MLL1) encodes a chromatin-modifying protein and was discovered as a result of the cloning of translocations involved in human leukemias. MLL1 is a histone lysine 4 (H3K4) methyltransferase that supports transcription of genes that are important for normal development includinghomeotic(Hox) genes.MLL1rearrangements result in expression of fusion proteins without H3K4 methylation activity but may gain the ability to recruit other chromatin-associated complexes such as the H3K79 methyltransferase DOT1L and the super elongation complex. Therefore, chromosomal translocations involvingMLL1appear to directly perturb the regulation of multiple chromatin-associated complexes to allow inappropriate expression of developmentally regulated genes and thus drive leukemia development.
authors.affiliation: Department of Pediatric Oncology, Dana Farber Cancer Institute, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts 02215.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Krivtsov
authors.affiliation: Department of Pediatric Oncology, Dana Farber Cancer Institute, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts 02215.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshii
authors.affiliation: Department of Pediatric Oncology, Dana Farber Cancer Institute, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts 02215.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000235:genetics* / Q000473:pathology; D051379:Mice; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*
chemical_list: D002843:Chromatin; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase