Clinical impact of SNP of P53 genes pathway on the adult AML patients

Abstract

Introduction: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes.

Aim: To study the impact of p53, p21, and mdm2 gene polymorphisms on the clinical outcome in adult AML patients treated at the National Cancer Institute (NCI) - Cairo University.

Methods: Forty-eight adult AML patients presented to the Medical Oncology Department, NCI, from April 2010 till November 2011. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving P53, MDM2, and P21 single-nucleotide gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism coupled analysis.

Results: The mean age was 35.7 years. After a median follow-up period of 12 months, 28 patients (58.4%) achieved complete remission (CR) and the overall survival (OS) was 8.7 months. Patients with homozygous Arg/arg at codon 72 of P53 had a better median OS months than Arg/Pro and Pro/Pro (13.4 vs. 8.4 vs. 1.5 months, respectively; P = 0.045). P53/p21 combination had a better median OS and disease-free survival (DFS) of 12.1 and 13.7 months for wild type cases (GG + Ser/ser) and 20.3 and 20.7 months for patients with either variant genes (GC + Ser/arg) compared with 1.1 and 1.9 months for patients with both variant genes (CC + arg/arg), (P = 0.037 and 0.004). The presence of wild genotype of either P21 or MDM2 may abolish the effect of P53 homozygous variant genotype on the OS. Neither p21nor mdm2 polymorphism alone showed an impact on OS or DFS. CR was not affected by any of the three gene polymorphisms.

Conclusion: The p53 pathway gene polymorphisms may affect the OS of adult AML patients.

Keywords: Acute myeloid leukemia; Clinical outcome; Polymorphism; mdm2; p21; p53 gene.