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Expression of protein-tyrosine phosphatases in Acute Myeloid Leukemia cells : FLT3 ITD sustains high levels of DUSP6 expression

Arora, Deepika (författare)
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
Köthe, Susanne (författare)
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
van den Eijnden, Monique (författare)
Merck Serono, Geneva 1202, Switzerland
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van Huijsduijnen, Rob Hooft (författare)
Merck Serono, Geneva 1202, Switzerland
Heidel, Florian (författare)
Department of Hematology/Oncology, Otto-von Guericke-University, Magdeburg, Germany
Fischer, Thomas (författare)
Department of Hematology/Oncology, Otto-von Guericke-University, Magdeburg, Germany
Scholl, Sebastian (författare)
Department of Hematology/Oncology, Clinic for Internal Medicine II, Jena University Hospital, Jena, Germany
Tölle, Benjamin (författare)
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
Böhmer, Sylvia-Annette (författare)
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
Lennartsson, Johan (författare)
Uppsala universitet,Ludwiginstitutet för cancerforskning
Isken, Fabienne (författare)
Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany
Müller-Tidow, Carsten (författare)
Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany
Böhmer, Frank-D (författare)
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
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 (creator_code:org_t)
2012
2012
Engelska.
Ingår i: Cell Communication and Signaling. - 1478-811X. ; 10:1, s. 19-
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Protein-tyrosine phosphatases (PTPs) are important regulators of cellular signaling and changes in PTP activity can contribute to cell transformation. Little is known about the role of PTPs in Acute Myeloid Leukemia (AML). The aim of this study was therefore to establish a PTP expression profile in AML cells and to explore the possible role of FLT3 ITD (Fms-like tyrosine kinase 3 with internal tandem duplication), an important oncoprotein in AML for PTP gene expression. PTP mRNA expression was analyzed in AML cells from patients and in cell lines using a RT-qPCR platform for detection of transcripts of 92 PTP genes. PTP mRNA 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 expressed PTP genes include PTPRC, PTPN2, PTPN6, PTPN22, DUSP1, DUSP6, DUSP10, PTP4A1, PTP4A2, PTEN, and ACP1. PTP expression was further correlated with the presence of FLT3 ITD, focusing on a set of highly expressed dual-specificity phosphatases (DUSPs). Elevated expression of DUSP6 in patients harboring FLT3 ITD was detected in this analysis. The mechanism and functional role of FLT3 ITD-mediated upregulation of DUSP6 was then explored using pharmacological inhibitors of FLT3 ITD signal transduction and si/shRNA technology in human and murine cell lines. High DUSP6 expression was causally associated with the presence of FLT3 ITD and dependent on FLT3 ITD kinase activity and ERK signaling. DUSP6 depletion moderately increased ERK1/2 activity but attenuated FLT3 ITD-dependent cell proliferation of 32D cells. In conclusion, DUSP6 may play a contributing role to FLT3 ITD-mediated cell transformation.

Nyckelord

Acute myeloid leukemia
Protein-tyrosine phosphatases
Dual-specificity phosphatases (DUSP)
mRNA expression
Fms-like tyrosine kinase (FLT3) with internal tandem duplication (ITD)
DUSP6
ERK signaling

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