Differences between nucleophosmin isoforms in de-novo acute myeloid leukemia: possible implications in developing targeted therapy for acute myeloid leukemia with normal karyotype

Background The current approach of treating de-novo acute myeloid leukemia (AML) is still ineffective. This is in part due to the clinical and molecular diversity of the disease. Accordingly, development of new effective targeted therapies for AML is mandatory. The current study investigated the differences between nucleophosmin (NPM) isoforms in de-novo AML. The work focused on AML with a normal karyotype as it constitutes 45% of AMLs and bears mutated nucleophosmin (mNPM). The main objective was to identify the active region in the NPM molecule to be targeted with a specific therapy. Materials and methods In this study human leukemia cell lines HL60 and OCI-AML3 were used as models for AMLs bearing wild-type NPM and mNPM, respectively. The study was conducted through indirect immunofluorescence and immunoblotting techniques. The obtained results were presented and analyzed with appropriate computer software. Results and conclusion The analyzed data proved, for the first time, that mNPM is phosphorylated at Thr199. As cdk2 is the main mediator of Thr199 phosphorylation, we speculated that a specific cdk2 inhibitor could be highly valuable as targeted therapy in de-novo AML with a normal karyotype. However, further experimental work in the presence of cdk2 inhibitors is needed.