Detection and assessment of the frequency of NPM1 and FLT3 ITD mutations in acute myeloid leukemia patients

Background and ObjectivesNPM1/Nucleophismin/B23 is a phosphoprotein with high expression in the proliferating cells. NPM1+AMLs are also frequently associated with FLT3 ITD mutations. The purposes of this study were to assess the frequency of NPM1 and FLT3 ITD mutations among Iranian AML patients and their correlation with FAB subtypes of AML. Materials and MethodsBone marrow and peripheral blood samples of 131 AML patients were randomly collected, and their DNA was then extracted. Afterwards, PCR was applied to the fragment of NPM1 gene with specific primers. PCR products were electrophoresed using CSGE method. In the end, the positive samples were sequenced to confirm the presence of NPM1 mutations. Furthermore, FLT3 ITD positive cases were screened using PCR and 2.5% agarose gel electrophoresis. ResultsOut of 131 patients, 23 (17.55%) (CI 95% = 0.107-0.244) were known to have NPM1 gene mutations. The highest frequency was among the subtypes of M4 (30.4%), M3 (21.7%), and M5 (13%). Also, 21 samples (16.03%) (CI 95% = 0.092-0.229) had FLT3 ITD mutations with 8 cases being NPM1 positive and other 13 NPM1 negative. ConclusionsNPM1 mutations are more frequent in monocytic subtypes (M4, M5). High frequency rates of NPM1 in M3 subtypes and allele D mutations in all subtypes together with the high degree of association between occurrence of NPM1 and FLT3 ITD mutations could be considered as interesting findings of the study (p=0.012).