AsianScientist (Dec. 14, 2015) – In a study published in Scientific Reports, researchers have identified a correlation between the protein nucleophosmin (NPM) and the development of an aggressive form of blood cancer called acute myeloid leukemia (AML). The findings mean that NPM may potentially become a target protein for future cancer therapy drug development.
AML is a cancer of the bone marrow and blood, in which abnormal blood cells are created. Red blood cells are responsible for carrying oxygen to tissues in the body, white blood cells fight infection and platelets stop bleeding by clotting the blood. Any abnormality in these cells can have devastating effects on these critical processes. AML is the most common form of blood cancer in adults and progresses very rapidly if left untreated.
While NPM has long been known as an important housekeeping gene that regulates various cellular functions in the body, its association with AML was only established in the last decade.
In earlier studies, the team led by Professor Lim Tit Meng from the Department of Biological Sciences at the National University of Singapore (NUS) established that NPM is vital for normal cell death and cell differentiation, and it was observed that mutated NPM actually inhibits programmed cell death.
While conducting further studies on the novel functions of the protein, Lim and PhD candidate, Ms. Narisa Chan, uncovered a puzzling phenomenon. They found that while about 50 to 60 percent of AML cells show abnormal chromosomes which contribute to genomic instability as a hallmark of cancer, a significant portion of AML cells (about 40 to 50 percent) possess normal-looking chromosomes.
Upon further investigation, they discovered that the mutated form of NPM—called NPMc—which is found in about one-third of AML cases, is associated with a novel cellular mechanism that develops AML cells containing normal chromosomes.
Centrosomes are responsible for the separation of chromosomes during cell division, a vital process for cellular and tissue development. Each human cell has 23 pairs or 46 chromosomes and when they divide, the resulting daughter cells must also contain the same number of chromosomes. Centrosomes are responsible for ensuring proper cell division and the separation of chromosomes.
The experimental results showed that the presence of NPMc could suppress centrosome reduplication which would otherwise result in unequal segregation of chromosomes during cell division and lead to genomic instability. The findings from this study therefore explained the prevalence of normal-looking chromosomes in AML cancer cells in about a third of AML cases.
With this new knowledge discovery, NPM may potentially become a target protein for future cancer therapy drug development. Lim and his team are currently looking to collaborate with clinician scientists to expand research into clinical sample investigations to further understand the cell biology involving NPM and NPMc.
The article can be found at: Chan et al. (2015) Cytoplasmic Nucleophosmin Has Elevated T199 Phosphorylation upon which G2/M Phase Progression is Dependent.
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Source: National University of Singapore.
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