Fig. 1
From: Therapeutic strategies against hDOT1L as a potential drug target in MLL-rearranged leukemias
Role of hDot1L in MLL related leukemogenesis. a MLL gene, which normally codes for H3K4 methyltransferase, undergoes chromosomal translocations and gets fused to more than 50 recurrent MLL translocation partners. These fusion partners interact with hDot1L and lead to mistargeting of hDot1L to MLL target genes like Hox gene cluster. Ectopic H3K79 methylation and the subsequent activation of the target genes results in leukemogenesis. b Small molecules that are capable of inhibiting the HMTase activity of would block H3K79 methylation and subsequent inhibition of leukemogenesis. c Another therapeutic strategy would be modulators that block the interaction of hDot1L with MLL fusion proteins. This would prevent ectopic H3K79 methylation and may lead to a novel treatment for MLL-related leukemogenesis. d Ectopic H3K79 methylation levels could be prevented by increasing the stability of untranslocated MLL1, thereby replacing the MLL-fusion chimeras