MLLT10 histone lysine methyltransferase DOT1L cofactor (MLLT10)

MLLT10 histone lysine methyltransferase DOT1L cofactor (MLLT10/AF10) is a 109-kDa chromatin-associated protein encoded on chromosome 10p12, belonging to a conserved family including AF17 and BR140. It contains PHD fingers, an extended PHD/LAP domain, AT-hook motif, nuclear localization signal, and a glutamine-rich C-terminal region. AF10 forms oncogenic fusion proteins through chromosomal translocations in leukemia, most prominently with CALM or MLL/KMT2A, generating aberrant transcription factors that drive malignant transformation by mislocalizing DOT1L. The resulting gene fusions dysregulate HOXA cluster genes and disrupt normal hematopoietic cell differentiation. AF10's normal biological functions include chromatin binding, transcriptional regulation, and interaction with DOT1L to mediate H3K79 methylation. Aberrant function, loss of key domains, or fusion with other proteins underlies its role in leukemia pathogenesis and provides a rationale for targeting DOT1L in therapy.

Other names

Protein AF-10AF10ALL1-fused gene from chromosome 10 proteinmyeloid/lymphoid or mixed-lineage leukemia; translocated to, 10type I AF10 proteintype III AF10 proteintype IV AF10 protein

Inhibition of DOT1L: prevents abnormal H3K79 methylation and subsequent dysregulation of HOXA cluster gene expression that drives leukemogenesis in MLLT10 fusion leukemias