Molecular study of KIT gene that is related to drug resistance in chronic myeloid leukemia patients

The KIT gene, known as proto-oncogene c-Kit, encodes a receptor tyrosine kinase and plays a crucial role in cellular processes through activation that initiates signal transduction pathways. The KIT protein includes five extracellular domains, a kinase domain, a transmembrane helix, and a juxta-membrane domain. The study investigated these domains in chronic myeloid leukemia (CML) patients, revealing insights that enhance clinical protocols for tyrosine kinase inhibitors used in targeted therapy for hematological malignancies. However, mutations in the kinase domain present challenges by impairing drug binding. In this exploratory investigation, mainly through PCR and Sanger sequencing techniques, 50 samples (30 patients and 20 controls) were utilized. A total of 27 mutations were identified. While the following mutations (G753C, G538C, A415T, and A404G) were the most frequent, (G814C, G858T, G876T, and G880A) were only found in control cohort. Interestingly, many unique mutations were detected in the Iraqi population, suggesting specific genetic polymorphisms. Furthermore, the data showed that younger patients had better responses to imatinib with fewer dangerous mutations, while middle-aged patients faced significant resistance, which correlated with weight gain and obesity. Elderly individuals displayed a higher mutation burden, necessitating multiple treatment changes. Despite limitations, this exploratory study stressed the importance of considering patients' genetic backgrounds and BMIs to improve therapeutic outcomes for CML patients.