Nat commun: scientists have found a new target for the treatment of acute myeloid leukemia

May 28, 2018 / BIOON / - MLL fusion gene represents a large class of leukemia driving factors, and its diversity mainly comes from the huge molecular heterogeneity of MLL C-terminal fusion partners Although studies on some MLL fusion proteins have revealed some key molecular pathways, the unified mechanism of all MLL fusion genes is still unclear Photo source: CeMM / Anna skucha, in order to reveal the mechanism, recently researchers from Austrian Academy of Sciences and other institutions, led by Professor Florian grebien, carried out a systematic study on the protein interaction among 7 remotely related MLL fusion proteins Their functional study of 128 conserved MLL fusion sites found that SETD2 plays a special role in MLL leukemia The absence of setd2 will lead to the growth restriction and differentiation of AML cells, and increase DNA damage In addition to its role in the trimethylation of H3K36, setd2 is also involved in maintaining the demethylation of H3K79 and the binding of MLL-AF9 to the key target gene (ruhoxa9) In combination with H3K79 methyltransferase inhibitor dot1l, the absence of setd2 can induce DNA damage, cell growth restriction, differentiation and apoptosis In general, these results reveal that MLL leukemogenesis depends on setd2, and reveal a new potential target for this cancer Reference: Anna skucha et al, MLL fusion driven leukemia requirements setd2 to safeguard generic integrity, nature communications (2018) Doi: 10.1038/s41467-018-04329-y