SETD2 in MLL-rearranged leukemia – a complex case

Abstract

Oncogenic MLL-fusion proteins often hijack essential molecular mechanisms during leukemogenesis. The histone methyltransferase SETD2 was implicated in the regulation of transcription, DNA damage and other cellular processes. Recent studies identified a critical role for SETD2 in MLL-rearranged leukemia. These results may help to unravel important functions of SETD2 in hematopoiesis.

SETD2-H3K36ME3: an important bridge between the environment and tumors

“…In addition, the demethylase inhibitor JIB-04 was shown to restore H3K36me3 levels by blocking H3K36me3 demethylation, thus enhancing the effects of chemotherapy (Sheng et al, 2019). After conditional knockout the SETD2 gene in MLL-AF9 AML mouse model, homozygous SETD2 loss was found to delay leukemogenesis, whereas heterozygous SETD2 loss resulted in accelerated disease progression and chemotherapy resistance (Mar et al, 2017;Skucha et al, 2018). Taken together, these studies provide evidence that SETD2 functions as a tumor suppressor in hematologic malignancies and that targeting the H3K36me3 demethylase may reverse chemotherapy resistance.…”