العلاقة بين التعدد الشكلي لجينة NUDT15 ذات الرقم ( rs116855232 ) والسمية النقوية المحرضة بمركبات البورين Mercaptopurine عند المرضى السوريين المشخص لديهم ابيضاض لمفاوي حاد
الكلمات المفتاحية:
NUDT15 polymorphism, Acute lymphoblastic leukemia, Mercaptopurine toxicity, Myelotoxicityالملخص
Background and Aims: NUDT15 genetic polymorphism is known to be associated with frequent hematopoietic toxicities during acute lymphoblastic leukemia (ALL) mercaptopurine therapy. The aim of this study is to test this association in a group of Syrian ALL patients.
Patients and Methods: This is a retrospective study that included all patients with acute lymphoblastic leukemia reaching at least 6 months of maintenance therapy between January 2018 and May 2020 at three recruitement sites in Damascus, Syria. The NUDT15 rs116855232 genetic polymorphism was performed and linked to the current clinical factors: 6-mercaptopurine dose intensity, early onset leukopenia, hepatotoxicity and therapy interruption.
Results: A total of 107 patients were enrolled (54.21% low-risk, 33.64% intermediate-risk and 12.15% high-risk). The mercaptopurine dose intensity was 82.61%, 56.90% and 4.99% for the genotypes CC, TC and TT respectively (P: 0.0071). A significant association was found between early onset neutropenia and NUDT15 polymorphism (TC or TT), OR: 8.92 (95% CI: 1.79-44.48, P: 0.012). None of the patients with NUDT15 polymorphism had significant liver transaminases elevation.
Conclusion: Our study confirms that NUDT15 rs116855232 polymorphism is associated with mercaptopurine hematopoietic toxicity but not with hepatotoxicity in a population of Syrian patients with ALL.
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