Publication Date:
2012-07-12
Description:
Protein-tyrosine phosphatases (PTPs) are important regulators of cellular signaling andchanges in PTP activity can contribute to cell transformation. Little is known about the roleof PTPs in Acute Myeloid Leukemia (AML). The aim of this study was therefore to establisha PTP expression profile in AML cells and to explore the possible role of FLT3 ITD (Fmsliketyrosine kinase 3 with internal tandem duplication), an important oncoprotein in AMLfor PTP gene expression. PTP mRNA expression was analyzed in AML cells from patientsand in cell lines using a RT-qPCR platform for detection of transcripts of 92 PTP genes. PTPmRNA expression was also analyzed based on a public microarray data set for AML patients.Highly expressed PTPs in AML belong to all PTP subfamilies. Very abundantly expressedPTP genes include PTPRC, PTPN2, PTPN6, PTPN22, DUSP1, DUSP6, DUSP10, PTP4A1,PTP4A2, PTEN, and ACP1. PTP expression was further correlated with the presence of FLT3ITD, focusing on a set of highly expressed dual-specificity phosphatases (DUSPs). Elevatedexpression of DUSP6 in patients harboring FLT3 ITD was detected in this analysis. Themechanism and functional role of FLT3 ITD-mediated upregulation of DUSP6 was thenexplored using pharmacological inhibitors of FLT3 ITD signal transduction and si/shRNAtechnology in human and murine cell lines. High DUSP6 expression was causally associatedwith the presence of FLT3 ITD and dependent on FLT3 ITD kinase activity and ERKsignaling. DUSP6 depletion moderately increased ERK1/2 activity but attenuated FLT3 ITDdependentcell proliferation of 32D cells. In conclusion, DUSP6 may play a contributing roleto FLT3 ITD-mediated cell transformation.
Electronic ISSN:
1478-811X
Topics:
Biology
,
Medicine
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