Abstract 2117: Changes of the DNA methylation status in multiple myeloma patients experiencing chemotherapy induced peripheral neuropathy
Authors: Natarajan Umamaheswari , Ahmed Sultan E. , Weinstein Steve , Rathinavelu Appu 
Published: June 2023

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is considered to be one of the most common side effects caused by anti-neoplastic agents (1) such as Bortezomib (BTZ), Cisplatin (CSP), Taxol (TAX), and Vincristine (VINC). Clinical manifestations of CIPN include deficits of varying intensities of sensory, motor, and autonomic functions. Growing evidence suggests that epigenetic alterations could strongly underlie the induction and maintenance of PN (Peripheral Neuropathy) caused by many factors, including chemotherapy. Recently, a few groups have reported epigenetic alterations as well as changes in the Gene Expression Profiles (GEP) using the DNA and RNA isolated from patients experiencing CIPN. Therefore, our goal was to determine epigenetic alterations that may serve as predictive biomarkers and/or diagnostic biomarkers in the DNA isolated from the Peripheral Blood Mononuclear Cells (PBMCs) of human patients who were exhibiting varying levels of CIPN. To obtain preliminary data, we analyzed the methylation status of the DNA isolated from 3 Multiple Myeloma (MM) patients who experienced different levels (grades 1-7) of CIPN. When the methylation status of the MM patients was analyzed, the DNA was differentially methylated in 12,230 regions, in comparison to a normal control. Out of the above-mentioned total, about 4,563 regions were hypermethylated and 7,667 regions were hypomethylated. These differentially methylated regions included CpG islands in the promoter, intronic, and exonic regions of various genes within the 23 pairs of chromosomes including X and Y. When the most enriched Gene Ontology (GO) terms were identified, about 20 of them exhibited DNA hyper-methylation with fold changes ranging from 1-4 with the highest significance of 2.0e-12. The ranking of the genes involved in the top 3 GO terms related to neuronal function revealed that a total of 112 were hypermethylated in all three patients compared to the control. Similarly, ranking of the genes in the top GO terms with the highest fold change of hypo-methylation revealed 176 genes. Though few other GO terms showed significant changes, they were excluded in our CIPN-related ranking analysis, because they appeared to be linked to cancer or cancer growth-related pathways. It appears that these 288 hyper or hypomethylated genes may be directly involved in the onset, progression, or maintenance of CIPN. Analysis of the functional significance of these genes would provide greater insight into the relevance of the methylation status and its impact on the functions of the neurons that might be involved in pre-disposing or causing CIPN. Our research outcomes are expected to facilitate the design of an assessment method to detect the onset and progression of CIPN in cancer patients. (This research was supported by the Community Foundation of Broward and the Royal Dames of Cancer Research Inc. of Ft. Lauderdale, Florida).

Citation Format: Umamaheswari Natarajan, Sultan E. Ahmed, Steve Weinstein, Appu Rathinavelu. Changes of the DNA methylation status in multiple myeloma patients experiencing chemotherapy induced peripheral neuropathy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2117.