Frequency of TP53 Mutations and its Impact on Drug Sensitivity in Acute Myeloid Leukemia?

The purpose of this study is to find out the frequency of TP53 mutations in acute myeloid leukemia (AML) patients and correlate sensitivity of drug response with TP53 mutations. In AML more than 90 % of cases comprise of wild type TP53. 94.2 % of TP53 mutations are found within exon 5-8 of which 73 % are point mutations. TP53 mutations were analysed with high resolution melting curve analysis. We analysed 106 AML samples of which we found nine mutations which represents 8.5 % mutation rate and found one rare SNP. The effect of TP53 mutations were studied on the chemosensitivity of two new drugs AZD115 and RHPS4, an Aurora Kinase B inhibitor and Telomerase inhibitor respectively. Four mutations were found out of 17 for RHPS4 stating significant (p = 0.002) increase in sensitivity and no mutation found in AZD1152 database, but need more study to get definite conclusion.