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Research Findings Focus on Characterizing the Epigenetic Landscape in Multiple Myeloma

By: Sarah Campen, PharmD
Posted: Tuesday, March 15, 2022

Jerome Moreaux, PhD, of the University of Montpellier, France, and colleagues have characterized the epigenetic landscape of human multiple myeloma cell lines for the first time. The researchers hope that a thorough understanding of the epigenetic modifications that are involved in the development and progression of multiple myeloma may advance the understanding of multiple myeloma pathophysiology. Their study was published in Theranostics.

“This study provides a comprehensive characterization of the [multiple myeloma] epigenetic landscape, representing a unique resource for future biological studies which could help in identifying novel critical epigenetic modifications involved in [multiple myeloma] progression and drug resistance,” stated the study authors.

In this study, the researchers generated chromatin immunoprecipitation sequencing maps to analyze histone mark changes on 16 human multiple myeloma cell lines. To represent the molecular heterogeneity of multiple myeloma across cell lines, four active histone marks (H3K4me1, H3K4me3, H3K27ac, and H3K36me3) and two repressive histone marks (H3K9me3 and H3K27me3) were selected for analysis.

Links between histone modifications and cytogenetic abnormalities or recurrent mutations were highlighted using differential analysis of histone modification profiles. The study authors identified super-enhancers associated with genes involved in multiple myeloma biology, as well as promoters of genes enriched in H3K9me3 and H3K27me3 repressive marks associated with potential tumor suppressor functions.

Dr. Moreaux and colleagues developed two distinct risk scores based on super-enhancers and repressive regions to identify patients with high-risk multiple myeloma in two independent cohorts—the CoMMpass cohort (n = 674) and Montpellier cohort (n = 69). They also identified epigenetic biomarkers based on H3K4me3 modification that may predict multiple myeloma cell response to lenalidomide and histone deacetylase inhibitors.

Disclosure: The study authors reported no conflicts of interest.

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