Disordered histone methylation in hematological malignancies the case of utx/kdm6a.

DISORDERED HISTONE METHYLATION IN HEMATOLOGICAL MALIGNANCIES THE CASE OF UTX/KDM6A. Trans Am Clin Climatol Assoc. 2018;129:24-36 Authors: Licht JD Abstract Alterations of epigenetic proteins that modulate the gene repressive lysine 27 on histone H3 (H3K27me) are recurrent features in cancers, including multiple myeloma (MM). The histone demethylase UTX/KDM6A, mutated in up to 10% of cases of MM activates genes by removing the H3K27me3 repressive histone mark, counteracting EZH2. RNA-sequencing studies showed that UTX upregulated genes in association with loss of H3K27me. Treatment of MM cell lines with an EZH2 inhibitor preferentially slowed growth of UTX-null cells. EZH2 inhibitors activated many of the same genes as UTX but also induced the earlier stage B cell marker Bcl6 which, in turn, shut off the late B cell IRF4 and MYC, leading to cell death. PMID: 30166694 [PubMed - in process]
Source: Transactions of the American Clinical and Climatological Association - Category: General Medicine Tags: Trans Am Clin Climatol Assoc Source Type: research