c.202G > A/c.376A > G G6PD Polymorphisms Increase the Risk of Fungal Infections in Acute Myeloid Leukemia Patients

Abstract

Introduction: Patients with acute myeloid leukemia (AML) show a higher risk for several types of infections, including fungal infections (FI), which are one of the main causes of morbidity and mortality. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme located in all cells that is very necessary in leukocytes for the production of basic and acid proteases that are used to destroy invading microorganisms. Our objective in this study was to evaluate whether polymorphisms in the G6PD gene concomitantly with FI are associated with clinical events and morbidity in patients diagnosed with AML and followed up at the Amazonas State Blood Center (HEMOAM), Manaus, Brazil. Materials and Methods: The study population was randomly constituted of adults and children, of either sex, and any age, with a diagnosis of acute myeloid leukemia, all of whom were undergoing treatment at the HEMOAM. Molecular genotyping was performed using real-time PCR (qPCR) and subsequent Sanger sequencing to confirm the c.202G > A/c.376A > G polymorphisms. Results: A total of 157 patients (91 (58%) males and 66 (42%) females) were involved in the study. The most prevalent AML subtype in the studied group was M3 in 63 patients (40.12%), followed by M5 in 33 patients (21.02%), M2 in 21 patients (13.37%) and M4 in 15 patients (9.55%), with a similar prevalence between genders. The prevalence of fungal infections was identical between genders; however, bruising (p = 0.004), vomiting (p = 0.016) and cardiac alterations (p < 0.001) were higher in females, while persistent cough (p = 0.049) and diarrhea (p < 0.001) were higher in males. A total of eighteen patients presents G6PD polymorphisms, with 8 (5.1%) of these for c.202GA/AA, 18 (11.5%) for c.376AG/GG and 4 (2.5%) for both polymorphisms concomitantly (c.202AA/c.376GG). However, the prevalence of death in patients affected with FI was much higher in those that have these polymorphisms (p < 0.001). Conclusion: We believe that the determination of G6PD polymorphisms will allow the development of monitoring strategies, and aid in early diagnosis and the appropriate and targeted treatment for AML. In addition, evaluating their activity may help to identify AML patients at a higher risk of FI, thus allowing the design of more intensive therapeutic and surveillance strategies.