Thus, although studies of SETD2-dependent processes in cancer have contributed to a better understanding of the SETD2⁻H3K36me3 axis, many open questions remain regarding its specific role in leukemia.
To clarify the impact of SETD2 mutations on chemotherapy sensitivity in MLLr leukemia, two loss-of-function (LOF) Setd2-mutant alleles (Setd2<sup>F2478L/WT</sup> or Setd2<sup>Ex6-KO/WT</sup>) were generated and introduced, respectively, to the Mll-Af9 knock-in leukemia mouse model.
The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases represent a prosurvival pathway that is upregulated in response to hypoxia, in a HIF-1-independent manner.
Histone methyltransferases, including MLL1, DOT1L, EZH2, and SETD2 are recurrently deregulated in human leukemia, either directly by gene mutations or balanced translocations, or indirectly as components of protein complexes that are disturbed in leukemia due to alterations of the other components in these complexes.