Characteristics of TP53 mutation in adult precursor B-cell acute lymphoblastic leukemia

Abstract

Objectives TP53 is the most intensively studied gene in cancer. However, data on the frequency and prognostic significance of TP53 mutations in acute lymphoblastic leukemia (ALL) are still lacking. This study aimed to determine the characteristics of TP53 mutation, its correlation with clinical and laboratory parameters and other cytogenetic alterations, and their impact on patient outcome on day 21 after induction therapy. Patients and methods This is a prospective cohort clinical study that was conducted on 41 de-novo adult ALL patients, who presented to the Hematology/Oncology Unit of Ain-Shams University Hospitals, where all studied patients were subjected to the treatment regimen. TP53 mutation was investigated in 41 patient samples using the RT-PCR. Results TP53 mutation was detected in 19.5% of studied cases. A highly significant association was detected between 17P deletion and TP53 mutation (P<0.0001). A significant association was detected between TP53 mutation and abnormal karyotyping (P=0.032). The authors found a clear association between TP53 mutation and hypodiploidy (P=0.001) and MYC rearrangements (P=0.001). In contrast, TP53 mutation was clearly underrepresented in ALL patients with t(9;22)(q34;q11). A highly significant association between TP53 mutation and the poor outcome on day 21 (P=0.002) was observed. The patients with TP53 mutation revealed either failure of remission (50%) or incomplete remission (50%). Logistic regression analysis of factors influencing the patient outcome showed that advanced age (>34 years), high total leukocyte count (>40 × 109/l), and abnormal fluorescence in-situ hybridization and karyotyping results due to cytogenetic abnormalities are independent predictors of poor outcome with failure of induction of complete remission on day 21. Conclusion TP53 alterations strongly identify high-risk adult precursor B-ALL patients with poor outcome in this study; yet, this needs further investigation on a larger sample size with a longer follow-up. Investigations of TP53 mutation especially in adult B-cell ALL (accounting 75% of adult ALL) may help with the selection of patients in need of intensive therapeutic strategy or may help with designation of new innovative targeted therapies.