Investigating the Impact of MYC Gene Promoter Methylation and IKZF۱ Gene Body Methylation on Disease Progression and Drug Resistance in High-Risk Multiple Myeloma Patients

Introduction Multiple myeloma (MM) is a hematologic neoplasm defined by the clonal proliferation of plasma cells within the bone marrow. While there have been significant advancements in treatment options, high-risk subtypes of multiple myeloma continue to present considerable challenges owing to their aggressive characteristics and resistance to therapy. Epigenetic modifications, especially DNA methylation, are pivotal in the pathogenesis of MM. This study aims to examine the specific effects of DNA methylation in the MYC gene promoter and the IKZF۱ gene body on disease progression and drug resistance in patients with high-risk MM. Methods We aim to analyze DNA methylation patterns in a cohort of high-risk multiple myeloma (MM) patients utilizing bisulfite sequencing and methylation-specific PCR techniques. Our focus is on the promoter region of the MYC gene and the body of the IKZF۱ gene. Additionally, we will assess the correlations between methylation levels and clinical parameters, including disease progression and treatment response . Over the past four decades, in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) models have seen significant advancements; however, the pharmaceutical industry continues to face challenges with late-stage toxicity failures of lead molecules. This issue of late-stage attrition in drug candidates due to adverse ADMET profiles has prompted us to examine the current role and status of various in silico tools. We will also explore the emergence of machine learning (ML) programs for ADMET prediction to evaluate the functional consequences of these methylation changes on gene expression and drug sensitivity. Results Aberrant hypermethylation of the MYC gene promoter is significantly linked to increased disease severity and a poorer prognosis. In contrast, methylation within the gene body of IKZF۱ is associated with reduced effectiveness of standard therapeutic agents, such as proteasome inhibitors and immunomodulatory drugs. Functional assays have shown that hypermethylation of the MYC promoter results in decreased MYC expression, whereas methylation of the IKZF۱ gene body hinders drug-induced apoptosis in multiple myeloma cell lines. Conclusion This study highlights the role of DNA methylation in modulating disease progression and drug resistance in high-risk MM. The identification of specific methylation biomarkers in the MYC and IKZF۱ genes provides valuable insights into the epigenetic landscape of MM and offers potential avenues for developing targeted therapeutic strategies. Future research should focus on translating these findings into clinical practice, with the aim of improving patient stratification and treatment outcomes.

کلیدواژه ها:

Multiple myeloma ، MYC ، IKZF۱ ، Methylation