Genetic Variations in BCL3, MDM4, KLF14, and miR-146a and Their Associations with the Predisposition and Progression of Myeloproliferative Disorder and Chronic Myeloid Leukemia Patients.

PMID 41378237 | PMCID PMC12688369 | DOI 10.1159/000545352 · Molecular syndromology · 2025 · View on PubMed ↗

INTRODUCTION: Prior research on the genotype and allele variations of immunometabolism genes and their correlations with the risk of myeloproliferative neoplasms (MPNs) and chronic myeloid leukemia (CML) is inconsistent. AIM: This study aimed to assess the correlations between mutations in specific immunometabolism genes with the risk and progression of MPN and CML in Saudi patients. METHODS: This case-control study included 244 Saudi patients, 122 patients with MPNs and CMLs, and 122 healthy controls. Immunometabolism genes, including BCL3 (rs2927488 G>A), MDM4 (rs11801299 G>A), KLF14 (rs972283 G>A), and miR-146a (rs2910164 C>G), were identified via tetra amplification-refractory mutation system PCR. RESULTS: In comparison to healthy persons, MPN and CML patients exhibited a higher prevalence of genotype and allele variants in immunometabolism genes, BCL3 rs2927488 G>A (0.027), MDM4 rs11801299 G>A (0.028), KLF14 rs972283 G>A (0.0004), and miR-146a rs2910164 G>C (0.004). DISCUSSION AND CONCLUSION: The prevailing inheritance model suggested that mutations in all four immunometabolism genes were significantly correlated with an elevated chance of developing MPNs, with increases of 1.84-, 2-, 4.28-, and 2.75-fold for BCL3, MDM4, KLF14, and miR-146a, respectively, in comparison to healthy controls. In addition, we assessed the effect of gene polymorphisms on the course of the disease, and rapid disease progression was found to be correlated with the presence of these polymorphisms. These findings could help determine the risk of developing MPNs and patient prognosis.