Neurological disorders concomitant with CML in patients taking Imatinib

Neurological disorders concomitant with CML in patients taking Imatinib
Negar Nouri,¹ Zahra Khalaj,² Erfan Zaker,³ Seyyed Mehdi Kalantar,⁴ Vali Allah Mehrzad,⁵ Mansoor Salehi,^6,*
1. student research committee, Shahid Sadoughi university of Medical Sciences, Yazd, Iran
2. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3. student research committee, Shahid Sadoughi university of Medical Sciences, Yazd, Iran
4. Medical Genetic Research and Clinical Centre for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5. Department of Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Introduction: Neurogenetics is a combination of genetic, neurology, psychology, and psychiatry which contributes to our complete understanding of differences in each individual. Neurogenetics communicates between genetic variants and individual differences in brain characteristics. Despite the advances in this field, there are still three challenges ahead, including: conducting research on individual variables with small effects, absence of detailed mechanisms and need to translate findings toward greater clinical relevance. The behavioral neurogenetics is a multi-stage study, which involves genetic factors, brain structure and function, neurobehavioral processes and environmental influences. Genetic conditions cause neurogenic disorders in children include fragile X, Turner, Klinefelter syndrome and etc. Imatinib is an oral tyrosine kinase inhibitor which impedes ABL and the BCR- ABL1 fusion protein in chronic myeloid leukemia (CML), c-KIT and the platelet- derived growth factor receptor (PDGFR) in gastrointestinal cancers (GIST). This drug causes hematologic response in 95% and major cytogenetic response in 60% of CML patients.
Methods: Central Nervous System Blast Crisis in Chronic Myeloid Leukemia on Imatinib Mesylate Therapy: Report of Two Cases. CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid. Isolated Central Nervous System Relapse in Lymphoid Blast Crisis Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Patients on Imatinib Therapy. An Unusual Presentation of Chronic Myelogenous Leukemia: A Review of Isolated Central Nervous System Relapse. Chronic myelogenous leukemia presenting with central nervous system infiltration, successfully treated with central nervous system-directed chemotherapy followed by allogeneic stem cell transplantation. Prophylaxis of central nervous system leukemia: a case of chronic myeloid leukemia with lymphoid blast crisis treated with imatinib mesylate. pubmed
Results: New studies have been shown that due to the presence of efflux transporters (such as ABCB1 and ABCG2) in blood-brain barrier, the activity of these transporters can be effective in responding to imatinib. So presence of non-functional variants in these transporters cause accumulation of blast crisis cells in central nervous system (CNS) addition to imatinib effects on the CNS of adult and fetal, it also affects their peripheral nervous system (PNS).
Conclusion: There are still contradictory results about the neurological effects of imatinib on CNS and PNS. So, further studies are needed to solve these discrepancies and improve the treatment of CML patients with concurrent CNS disorders.
Keywords: "Neurogenetics" "Imatinib" "chronic myeloid leukemia"