期刊
BLOOD
卷 111, 期 7, 页码 3859-3862出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-06-098251
关键词
-
类别
资金
- NATIONAL CANCER INSTITUTE [R01CA071692, R37CA071692] Funding Source: NIH RePORTER
- NCI NIH HHS [CA-71692, R37 CA071692, R01 CA071692] Funding Source: Medline
Nucleophosmin (NPM1) gene has been heavily implicated in cancer pathogenesis both as a putative proto-oncogene and tumor suppressor gene. NPM1 is the most frequently mutated gene in acute myeloid leukemia (AML), while deletion of 5q, where NPM1 maps, is frequent in patients with myelodysplastic syndromes (MDS). We have previously shown that mice heterozygous for Npm1 (Npm1(+/-)) develop a hematologic syndrome with features of human MDS. Here we analyzed Npm1(+/-) mutants to determine their susceptibility to cancer. Npm1(+/-) mice displayed a greater propensity to develop malignancies compared with Npm1(+/+) mice. The Npm1(+/-) cohort frequently developed hematologic malignancies of both myeloid and lymphoid origin with myeloid malignancies displaying the highest incidence. Malignant cells retained the wild-type allele with normal localization and expression of Npm1 at the protein level, suggesting that complete Npm1 loss is not a prerequisite for tumorigenesis. Our results conclusively demonstrate that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据