Nucleophosmin Gene Mutation in Acute Myeloblastic Leukemia: Apoptotic Role

Abstract

Introduction and objectives: Since Falini and his co-workers reported the expression of nucleophosmin (NPM) gene mutation in acute myeloblastic leukemia (AML), and various research in succession clarified the role of mNPM in AML. We previously studied the proliferative role of mNPM in AML in a trial to discover its role in AML development and leukemogenesis. This study aimed to complete the scenario and investigate the apoptotic role of mNPM AML. Another objective was to assess the effect of NPM mutational state on response to etoposide treatment in AML. Materials and methods: In this study human leukemia cell lines, HL60 and OCI-AML3 were used as models for AMLs bearing wild type (wt) and mutated (m) NPM, respectively. The study was conducted by using viability studies. The obtained results were reaffirmed by immunocytochemical and immunoblotting analyses. Results were interpreted and presented with the appropriate computer softwares. Results and conclusions: Interpretation of data showed normal growth and delayed apoptotic response of etoposide treated cells bearing mNPM as compared with cells carrying wtNPM and the control. Also we noted irreversible cytoplasmic translocation of NPM that was dependent on the duration and extent of the etoposide induced cytotoxicity in cells with wtNPM. Proteomic analysis of NPM revealed that protein expression in the etoposid lysates was approximately similar to the untreated controls We concluded that wtNPM has a pro-apoptotic effect while mNPM has an anti-apoptotic effect, suggested that therapeutic response to etoposide treatment in AML could be variable from one patient to another depending on the molecular basis of leukemia development in each case. Also, it was concluded that AML cells bearing nucleophosmin mutation are resistant to etoposide effect.