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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3142-3149.
Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-10-4057.
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Submitted October 25, 2004
Accepted June 11, 2005
Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia
Rongzhen Xu, Yingzi Yu, Shu Zheng, Xiaoying Zhao, Qinghua Dong, Zhiwen He, Yun Liang, Qinghua Lu, Yongmin Fang, Xiaoxian Gan, Xiaohua Xu, Suzhan Zhang, Qi Dong, Xiaohong Zhang, and Gen-Sheng Feng*
Department of Hematology, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang, China; Cancer Institute, Zhejiang University, Hangzhou, Zhejiang, China
Department of Hematology, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang, China
Cancer Institute, Zhejiang University, Hangzhou, Zhejiang, China
Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China
Cancer Institute, Zhejiang University, Hangzhou, Zhejiang, China; Cancer Research Center, The Burnham Institute, La Jolla, CA, USA
* Corresponding author; email: gfeng{at}burnham.org.
Shp2 tyrosine phosphatase plays a critical role in hematopoiesis and dominant active mutations have been detected in the human gene PTPN11, encoding Shp2, in child leukemia patients. We report here that although no such mutations were detected in 44 adult leukemia patients screened, Shp2 expression levels were significantly elevated in most leukemia cell lines and primary leukemia cells, as compared to normal hematopoietic progenitor cells. The Shp2 protein amounts correlated well with the hyperproliferative capacity but were inversely associated with the differentiation degree of leukemia cells. Suppression of Shp2 expression induced apoptosis and inhibition of leukemic cell clonogenic growth. Notably, the majority of Shp2 was preferentially localized to the plasma membrane and was constitutively phosphorylated on tyrosine in leukemia cells, and also in normal hematopoietic cells following mitogenic stimulation. Based on these results, we propose that aberrantly increased expression of Shp2 may contribute, collaboratively with other factors, to leukemogenesis.
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