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Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-04-1308.
Submitted April 28, 2003
Accepted July 22, 2003
PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells
Ming-jiang Xu, Xingwei Sui, Runxiang Zhao, Chunhua Dai, Sanford B Krantz, and Zhizhuang Joe Zhao*
Department of Medicine, Department of Veterans Affairs Medical Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
* Corresponding author; email: joe.zhao{at}vanderbilt.edu.
Polycythemia vera (PV) is a human clonal hematological disorder. Previously we demonstrated that erythroid colony-forming cells (ECFCs) from PV patients contained a hyperactive membrane-associated tyrosine phosphatase. We now show that this phosphatase corresponded to PTP-MEG2, an intracellular enzyme with a putative lipid-binding domain. The increased activity of PTP-MEG2 in PV cells is due to its elevated distribution in the membrane fraction. With the development of ECFCs to mature red cells, the protein level of PTP-MEG2 decreased gradually, but membrane-associated PTP-MEG2 was sustained for a longer period of time in PV cells, which correlated with an enhanced colony forming capability of the cells. Importantly, expression of dominant negative mutant forms of PTP-MEG2 suppressed in vitro growth and expansion of both normal and PV ECFCs. The data indicate that PTP-MEG2 has an important role in the development of erythroid cells.
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