Nucleophosmin overexpression can prevent centrosome reduplication
13 Sep 2015 Scientists in NUS found another novel function of the nucleoprotein called nucleophosin in the physiology of acute myeloid leukemia.
A team led by Prof LIM Tit Meng from the Department in Biological Sciences in NUS has found yet another novel function of the nucleoprotein called nucleophosmin (NPM) in the physiology of acute myeloid leukemia (see Figure) which is an aggressive form of blood cancer. The discovery can help explain how more than 50% of Acute myeloid leukemia (AML) cells under the microscope appear to have a normal karyotype, i.e., the chromosomes look normal while the cells are cancerous.
The team has earlier published a paper in 2010 in the prestigious journal Blood describing how the mutant NPM actually inhibits programmed cell death as a caspase enzyme inhibitor. The blood cell differentiation is also inhibited. The mutation hence contributes to the cancerous state of the blood cells. This latest publication shows a new discovery that NPM also has a role to play in centrosome duplication as the increased cytoplasmic load of NPM due to its mutation can prevent centrosome reduplication thereby maintaining the normal karyotype.
AML is a deadly disease and the understanding of the functions of NPM may lead to better diagnostics and also potential therapeutic strategy targeted at normalizing the physiology due to NPM overexpression in the blood cells.
Figure shows acute myeloid leukemia.
1. Chan N, Lim TM. Cytoplasmic nucleophosmin has elevated T199 phosphorylation upon which G2/M phase progression is dependent. Scientific Reports (2015, in press)
2. Leong SM, BX Tan, BA Baidah, T Yan, LY Chee, ST Ang, KG Tay, LP Koh, Yeoh EJ, ESC Koay, HYK Mok, TM Lim “Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive Caspase‑6 and ‑8 inhibition.” Blood (2010) 116 (17) 3286.