Klin Onkol 2007; 20(6): 390-396.
Backgrounds: Nucleophosmin (NPM) is an abundant multifunctional phosphoprotein with both tumor-suppressor and oncogenic functions. NPM plays a key role in ribosome biogenesis, supporting cell growth and proliferation. NPM maintains genomic stability by controlling DNA repair mechanisms and centrosome duplication. NPM modulates the stability and the activity of the tumor suppressor p53 and is involved in the apoptotic response to stress and oncogenes action, thus contributing to the modulation of growth-suppressive pathways. Chromosomal translocations involving the NPM1 gene were found in myeloid and lymphoid cancers. The fusion proteins inhibit the activity of low levels of wild type NPM1 and this event induces tumorigenesis. However, NPM behaves as an tumor suppressor in tumors when NPM expression is reduced and its subcellular distribution altered. NPM1 is also
frequently overexpressed in both solid tumors and lymphoid cancers. The increased levels of NPM promote increased accumulation of alternative reading frame (ARF) in an inactive nucleolar state, inhibit p53 activation and stimulate growth. The p53 pathway is a target of anti-cancer therapeutics. Heterozygous mutations of NPM1 gene are the most frequent genetic lesions in acute myeloid
leukemia with normal karyotype. Design: The analysis of contemporary knowledge about nucleophosmin and its role in cancer and understanding of its signifi cance in oncogenesis is necessary for the development of new target procedures in therapy of cancer. Conclusions: Detection of NPM1 mutations allows to divide the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Understanding of the mechanism how mutant NPM1 effects leukemogenesis will facilitate the development of new chemotherapeutic agents. NPM1 overexpression can be used as one of tumor markers in carcinomas and lymphoid malignancies. The method of small interferent RNA (siRNA) employment represents a promise of a new strategy in anaplastic large cell lymphoma with chromosomal translocation t(2;5) treatment.
