Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia.
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 primary leukemia cells and leukemia cell lines, as compared with 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.
Xu
Rongzhen
R
Department of Hematology, Second Affiliated Hospital, School of Medicine, Cancer Institute, Zhejiang University, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310009, China. xurongzhen@hzcnc.com
Yu
Yingzi
Y
Zheng
Shu
S
Zhao
Xiaoying
X
Dong
Qinghua
Q
He
Zhiwen
Z
Liang
Yun
Y
Lu
Qinghua
Q
Fang
Yongmin
Y
Gan
Xiaoxian
X
Xu
Xiaohua
X
Zhang
Suzhan
S
Dong
Qi
Q
Zhang
Xiaohong
X
Feng
Gen-Sheng
GS
D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D022423:Myeloid Cells / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases