E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia

Cytarabine (Ara-C) plays an irreplaceable role in the treatment of acute myeloid leukemia (AML). However, there are significant differences in efficacy among patients. Our previous studies found that E2F1 rs3213150 polymorphism was associated with remission rate of Ara-C chemotherapy, but the specific mechanism is not clear. This study aimed to further confirm the correlation between E2F1 rs3213150 polymorphism and Ara-C resistance and prognosis in AML patients, and to provide valuable information for elucidating the molecular mechanisms involved.

Rs3213150 genotyping was performed in 922 AML patients by Sanger sequencing, and the effects of different genotypes on chemosensitivity and prognosis were analyzed by Logistic regression and Cox regression. Meanwhile, a prediction model of Ara-C chemotherapy resistance was established. The impact of rs3213150 polymorphism on E2F1 expression level was determined by luciferase reporter gene assay, and differentially expressed genes between patients with different genotypes were identified by RNA sequencing.

Compared with rs3213150 G allele carriers, patients with AA genotype had more obvious Ara-C resistance (41.94% vs. 27.94%, P = 0.002), shorter overall survival (529 d vs. 644 d, P = 0.008) and disease-free survival (519 d vs. 556 d, P = 0.023). Rs3213150G > A mutation resulted in decreased E2F1 expression.

E2F1 rs3213150 polymorphism influences the chemosensitivity and prognosis of Ara-C in Chinese AML patients.