期刊
LABORATORY INVESTIGATION
卷 91, 期 9, 页码 1298-1303出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2011.96
关键词
ALCL; lymphoma; mouse model; NPM-ALK; NPM1
资金
- Cancer Research UK [C19666]
- Wellcome Trust
- MRC [G0800784] Funding Source: UKRI
- Medical Research Council [G0800784B, G0800784] Funding Source: researchfish
Heterozygous expression of Nucleophosmin (NPM1) predisposes to hematological malignancies in the mouse and cooperates with Myc in lymphomagenesis. NPM1 is therefore regarded as a haploinsufficient tumor suppressor. Heterozygous loss of NPM1 occurs as a result of the t(2;5), which generates the oncogenic fusion tyrosine kinase, NPM-anaplastic lymphoma kinase (ALK), a molecule underlying the pathogenesis of anaplastic large cell lymphoma (ALCL). Given the aforementioned role of NPM1 as a tumor suppressor, we hypothesized that NPM1 heterozygosity would cooperate with NPM-ALK in lymphomagenesis. In the event, we observed no difference in tumor latency, incidence or phenotype in NPM-ALK-transgenic mice heterozygous for NPM1 relative to transgenic mice expressing both NPM1 alleles. We propose that although the t(2;5) simultaneously reduces NPM1 allelic dosage and creates the NPM-ALK fusion protein, the two events do not cooperate in the pathogenesis of ALCL in our mouse model. These data indicate that a tumor-suppressive role for NPM1 may depend on cellular and/or genetic context. Laboratory Investigation (2011) 91, 1298-1303; doi: 10.1038/labinvest.2011.96; published online 27 June 2011
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