Mixed-Lineage Leukemia Fusions and Chromatin in Leukemia | Zendy

Andrei V. Krivtsov | Zendy; Takayuki Hoshii | Zendy; Scott A. Armstrong | Zendy

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Mixed-Lineage Leukemia Fusions and Chromatin in Leukemia

Author(s) -

Andrei V. Krivtsov,

Takayuki Hoshii,

Scott A. Armstrong

Publication year - 2017

Publication title -

cold spring harbor perspectives in medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.853

H-Index - 105

eISSN - 2472-5412

pISSN - 2157-1422

DOI - 10.1101/cshperspect.a026658

Subject(s) - chromatin , biology , histone methyltransferase , homeotic gene , hox gene , genetics , chromatin remodeling , gene , transcription factor

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 including homeotic ( Hox ) genes. MLL1 rearrangements 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 involving MLL1 appear to directly perturb the regulation of multiple chromatin-associated complexes to allow inappropriate expression of developmentally regulated genes and thus drive leukemia development.

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