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Epigenetic Regulation of Oncogenic Overexpression of ITGB7 in Myeloma Cells

By: Julia Fiederlein Cipriano
Posted: Friday, March 24, 2023

According to Samrat Roy Choudhury, PhD, MSc, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues, the expression of integrin β7 (ITGB7) seems to be epigenetically enhanced in high-risk molecular subgroups of patients with multiple myeloma. The results of this analysis were published in the journal Clinical Epigenetics.

ITGB7 expression regulated by the transcription factor cMAF and its function in bone marrow adhesion have been relatively well illustrated in multiple myeloma,” the investigators remarked. “[However], recent reports have shown that epigenetic mechanisms play a critical role in the process of cell adhesion–mediated drug resistance.”

The expression profiles of adhesion-related genes were analyzed in a cohort of patients with multiple myeloma and major IGH translocations or hyperdiploidies; they were diagnosed at the stage of premalignant monoclonal gammopathy of undetermined significance (n = 103), smoldering multiple myeloma (n = 190), or multiple myeloma (n = 53). Across the disease stage subgroups, ITGB7 was found to be significantly upregulated in patients with t(14;16) and t(14;20) translocations (P < .05); however, according to the investigators, it was sporadically upregulated in those diagnosed with multiple myeloma who harbored a t(4;14) translocation.

The investigators noted that, although ITGB7 appeared to be under trimethylated H3K27 repression in B cells, it acquired an active enhancer state in patients with t(4;14) translocations and a super-enhancer state in those with t(14;16) translocations. Targeted induction of DNA methylation at the ITGB7 super-enhancer was found to further upregulate the gene, whereas inhibition of the ITGB7 super-enhancer–associated transcription factor bromodomain-containing protein 4 appeared to downregulate its expression.

“Future studies should be aimed at designing target-specific inhibitors of cMAF or super-enhancer–associated transcription factors at the ITGB7 enhancer loci,” the investigators concluded. “Future studies are [also] warranted to investigate whether bromodomain-containing protein 4 inhibitors may be repurposed as therapeutic options for cell adhesion–mediated drug resistance.”

Disclosure: The study authors reported no conflicts of interest.

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