Characteristics of Acute Myeloid Leukemia Patients with TP53 Alterations

Abstract

Abstract Background TP53 is the most intensively studied gene in cancer. The vast majority of de novo AML patients have unaltered TP53 alleles; data from The Cancer Gene Atlas including adult patients with AML documented that ∼ 8% of cases harbor TP53 alterations. Objectives The objective of this study is to identify the features of TP53 alterations in acute myeloid leukemia (AML) patients, investigate its association with clinical findings, standard laboratory tests, morphological, cytogenetic and molecular profiles, and assess its influence on the overall outcome of patients on day 28 after induction therapy. Subjects and Methods The present study is an analytical observational study that was conducted on 60 de novo adult AML patients who presented to the Hematology/Oncology unit of Ain Shams University Hospitals. All patients’ samples were analyzed for TP53 deletion using LSI 17p13 FISH probe for detection of p53 deletion and they were further subjected to testing for TP53 Pro72Arg alterations by real time polymerase chain reaction. All patients were subjected to therapy and then followed up at day 28 to asses the outcome. Results Male gender and lower TLC were significantly associated with good outcome with (P-value ≤ 0.05). Patients with cytogenetic structural abnormalities showing 17q rearrangement showed significant association with bad outcome with (P-value ≤ 0.05) and t(8;21) was found to be highly significant in association with good outcome with (P-value< 0.01). FLT3ITD mutation was found to be highly significant in association with bad outcome with (P-value< 0.01). NPM mutation was significant in association with good outcome with (P-value ≤ 0.05). TP53 mutation was detected in 11.7 % of studied patients where 8.3% out of them were heterozygous mutation and 3.4% were homozygous. P53 mutation wassignificantly associated with advanced age, male gender and higher TLC with (P- value ≤ 0.05). Cytogenetic structural abnormalities including 11q23 rearrangement showed significant association with P53 mutation with (P-value ≤ 0.05) and t(8;21)+del 17p, del 17p& -7 and del 17p only was found to be highly significant in association with p53 mutation with (P-value< 0.01). Normal karyotyping showed negative relation with P53 mutation with (P-value ≤ 0.05) where all patients who yielded normal karyotyping (35%) were negative for P53 alterations; that doesn't necessarily denote causation, but it's an observable pattern, and del 17p that was found to be highly significant in association with p53 mutation with (P-value< 0.01). P53 mutation was found to be highly significant in association with bad outcome with (P-value < 0.01). Unfavorable and Favorable risk stratification of ELN 2022 were found to be highly significant in association with p53 mutation with (P-value< 0.01). ELN 2022 risk stratification categories were found to be highly significant in association with patients’ outcomes with (P- value < 0.01). Conclusion TP53 alterations strongly identify high-risk AML patients with poor outcome in this study yet, this needs further investigation on larger sample size with longer follow up. Investigations of TP53 mutation especially in Adult AML may help with the selection of patients in need of intensive therapeutic strategy or may help with designation of new innovative targeted therapies. Key words Tp53, Mutation, Adult Acute Myeloid Leukemia.