Clinical implication of nucleophosmin gene mutation and Flt-3 internal tandem duplication in a cohort of Egyptian AML patients
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- Khorshied, M.M., Said, W.A. & Shaaban, H.A.M. Comp Clin Pathol (2013) 22: 497. doi:10.1007/s00580-012-1439-0
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Nucleophosmin (NPM) gene mutations are the most frequent genetic abnormality in adult AML. NPM gene mutation (NPM1) leads to aberrant localization of the NPM protein into the cytoplasm. As NPM1 mutation is frequently associated with FMS-like tyrosine kinase 3—internal tandem duplication (FLT3-ITD) that appears to abrogate its favorable prognostic effect. This study aimed at detecting the frequency of NPM1 exon-12 gene mutation and FLT3-ITD in 62 de novo AML patients by reverse-transcriptase polymerase chain reaction and immunocytochemical staining. Twenty age- and sex-matched healthy volunteers were included in the current study as a control group. NPM1 mutation was detected in 30/62 (48.3%) of cases, while 27/62 (43.5%) of cases were FLT3-ITD-positive. All the control subjects were negative for the studied genetic mutations. Immunostaining for NPM revealed cytoplasmic positivity (NPMc+) in 32/62 (51.6%) of case. NPM1 mutation was significantly higher in patients with normal karyotype, FAB-M4 subtype, low expression of CD34 and favorable response to induction therapy. FLT3-ITD was higher among female patients and was associated with poor response to induction therapy. Patients harboring both mutations showed unfavorable response as the presence of FLT3-ITD abolished the favorable effect of NPM1. In conclusion, all AML cases should be screened prior to therapy for both mutations as two important prognostic markers that can be valuable in predicting the response to therapy, in addition to their role in monitoring minimal residual disease and early detection of relapse. Furthermore, they represent potential therapeutic targets.