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Type of publication: Journal Article
Type of document: Review Article

Year: 2019

Authors: Skucha, A; Ebner, J; Grebien, F

Title: Roles of SETD2 in Leukemia-Transcription, DNA-Damage, and Beyond.

Source: Int J Mol Sci. 2019; 20(5): 1029.



Authors Vetmeduni Vienna:

Grebien Florian

Vetmed Research Units
Institute for Medical Biochemistry


Abstract:
The non-redundant histone methyltransferase SETD2 (SET domain containing 2; KMT3A) is responsible for tri-methylation of lysine 36 on histone H3 (H3K36me3). Presence of the H3K36me3 histone mark across the genome has been correlated with transcriptional activation and elongation, but also with the regulation of DNA mismatch repair, homologous recombination and alternative splicing. The role of SETD2 and the H3K36me3 histone mark in cancer is controversial. SETD2 is lost or mutated in various cancers, supporting a tumor suppressive role of the protein. Alterations in the SETD2 gene are also present in leukemia patients, where they are associated with aggressive disease and relapse. In line, heterozygous SETD2 loss caused chemotherapy resistance in leukemia cell lines and mouse models. In contrast, other studies indicate that SETD2 is critically required for the proliferation of leukemia cells. 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. Here, we review the current literature about critical functions of SETD2 in the context of hematopoietic malignancies.

Keywords Pubmed: Animals
Carcinogenesisgeneticspathology
DNA Damage
Histone-Lysine N-Methyltransferasemetabolism
Humans
Leukemiageneticspathologytherapy
Mutationgenetics
Transcription, Genetic

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