SETD2 loss of function is a recurrent event in advanced-phase chronic myeloid leukemia and contributes to genomic instability: SETD2 loss in Chronic Myeloid Leukemia.

ABSTRACT: The SETD2 tumour suppressor encodes a histone methyltransferase that specifically trimethylates histone H3 on lysine 36 (H3K36me3), a key histone mark implicated in the maintenance of genomic integrity among other functions. We found that SETD2 protein deficiency, mirrored by H3K36me3 deficiency, is a nearly universal event in advanced-phase chronic myeloid leukemia (CML) patients. Similarly, K562 and KCL22 cell lines exhibited markedly reduced or undetectable SETD2/H3K36me3 levels, respectively. This resulted from altered SETD2 protein turnover rather than mutations or transcriptional downregulation, and proteasome inhibition led to the accumulation of hyper-ubiquitinated SETD2 and to H3K36me3 rescue suggesting that a functional SETD2 protein is produced but abnormally degraded. We demons

SUBMITTER: Mancini M 

PROVIDER: S-EPMC12022228 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature