Profiling Tyrosine Kinase Inhibitor-Specific Signatures of Homocysteine Metabolism and Mineral Homeostasis in Chronic Myeloid Leukemia

Abdulla, Kawakeb N; Hade, Istikrar M.; Jumaa, Azal Hamoody; Hussein, Shallal Murad; Abdulkareem, Ahmed Hazem; Yasin, Youssef Shakuri

doi:10.31557/APJCP.2026.27.10.3755

Profiling Tyrosine Kinase Inhibitor-Specific Signatures of Homocysteine Metabolism and Mineral Homeostasis in Chronic Myeloid Leukemia

Document Type : Research Articles

Authors

¹ Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq.

² College of Health and Medical Techniques, Al- Bayan university, Iraq.

³ Bilad Alrafidain University, Iraq.

10.31557/APJCP.2026.27.10.3755

Abstract

Background: The application of tyrosine kinase inhibitors (TKIs) has revolutionized the management of chronic myeloid leukemia (CML), rendering it a controllable disease. However, long-term administration is associated with adverse metabolic effects, particularly disruptions in homocysteine metabolism and mineral balance. A comprehensive comparison across TKI types remains absent. Objective: This study systematically characterized and compared the metabolic signatures elicited by first- and second-generation TKIs Imatinib, Nilotinib, and Dasatinib on homocysteine and mineral parameters in chronic myeloid leukemia. Methods: This retrospective cross-sectional study involved 90 stable CML patients treated with TKI therapy for at least six months at Baghdad Oncology Teaching Hospital between March 2024 and April 2025. Patients were divided into three equal groups based on their medication: Imatinib, Nilotinib, or Dasatinib. Fasting blood samples were collected and analyzed for homocysteine, PTH, calcium, potassium, creatinine, vitamin B12, and ALP. Statistical methods, including ANOVA and correlation analyses, were used to compare groups and explore drug-specific effects. Results: The three TKI groups demonstrated distinct metabolic disturbance patterns. Nilotinib was associated with the highest homocysteine levels and showed strong positive correlations with PTH and ALP. Dasatinib caused a moderate elevation in homocysteine and uniquely correlated positively with potassium. Imatinib showed the most favorable homocysteine profile, which was primarily inversely correlated with calcium. Multivariate analysis confirmed that these metabolic profiles effectively distinguished the three TKI groups. Conclusion: The present study demonstrates that Imatinib, Nilotinib, and Dasatinib elicit distinct and discernible metabolic signatures. These results support the adoption of personalized, TKI-specific monitoring approaches in the management of CML, aiming to proactively reduce long-term cardiovascular and skeletal adverse effects and thereby improve alignment between the quality and duration of survival.

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