Role of Nucleophosmin Gene Mutation in Leukemogenesis of Acute Myeloid Leukemia

Abstract

Background: Acute myeloid leukemia (AML) is a hematopoietic stem cell disorder that carries very poor prognosis. Understanding molecular basis of AML leukemogenesis could lead to the emergence of effective targeted therapies for AML. AML bearing nucleophosmin (NPM) gene mutation has distinct features. This study was conducted to investigate the role of mutated (m) NPM in pathogenesis of de novo AML through studying its contribution in proliferation of AML cell line cells.

Methods: Two types of human leukemia cell lines were used. One of them was a model for AMLs with mNPM and the other for AMLs with wild type (wt) NPM. Assessment of the proliferative role of mNPM in AML was carried out using cell culture and viability studies. The obtained results were reaffirmed by immunocytochemical and immunoblotting techniques.

Results: Analysis of results was done with the appropriate computer software. It showed higher proliferative potential of cells with mNPM compared to those bearing wtNPM only. Furthermore, the immunocytochemical studies demonstrated subcellular localization of NPM isoforms during various phases of mitosis. Mitosis was associated with cytoplasmic translocation of wtNPM in certain phases, while localization of mNPM remained unchanged throughout the cell cycle. Results of immunoblotting showed little or no change in protein expression of either NPM moieties during mitosis.

Conclusions: The current study demonstrated important contribution of NPM gene mutation in enhancing proliferation of AML cell lines. These results confirmed the role of mNPM in AML leukemogenesis, and highlighted the importance of targeting mNPM in new evolving AML therapies.




J Hematol. 2018;7(1):7-13
doi: https://doi.org/10.14740/jh365w