%0 Journal Article
%T Expression of protein-tyrosine phosphatases in Acute Myeloid Leukemia cells: FLT3 ITD sustains high levels of DUSP6 expression
%A Deepika Arora
%A Susanne K£¿the
%A Monique van den Eijnden
%A Rob van Huijsduijnen
%A Florian Heidel
%A Thomas Fischer
%A Sebastian Scholl
%A Benjamin T£¿lle
%A Sylvia-Annette B£¿hmer
%A Johan Lennartsson
%A Fabienne Isken
%A Carsten M¨¹ller-Tidow
%A Frank-D B£¿hmer
%J Cell Communication and Signaling
%D 2012
%I BioMed Central
%R 10.1186/1478-811x-10-19
%X In Acute Myeloid Leukemia (AML), cells in the bone marrow, which normally give rise to functioning blood cells like monocytes, have stopped their differentiation at an early immature state. Moreover, the cells divide rapidly and are largely autonomous, i.e. independent form extracellular signals, in their capacity to proliferate. The molecular reasons for these defects are only partially understood. An important oncoprotein, which drives proliferation of leukemic cells in a subset of AML patients, is named FLT3 ITD. ITD (internal tandem duplication) stands for a molecular alteration which makes this molecule, an enzyme catalyzing the transfer of phosphate from ATP to tyrosine residues of proteins (a protein-tyrosine kinase), highly and constitutively active. This leads to many alterations in the affected cells, including the re-programming of gene expression. In this study we have analyzed most members of an enzyme family designated protein-tyrosine phosphatases (PTPs, enzymes which revert the action of protein-tyrosine kinases by removing phosphate residues from phosphorylated tyrosines) for their abundance in AML cells. Highly expressed PTPs may play a contributing role for leukemic cell proliferation, lowly expressed members may be required for regulation of normal cell proliferation. We observed that among the analyzed 92 genes, one particular PTP designated DUSP6 is selectively highly expressed in such AML cells which also harbor the oncoprotein FLT3 ITD. Functional studies suggest that this PTP seems to contribute to the undesired cell proliferation driven by FLT3 ITD. It may therefore be an interesting candidate as drug target.Protein-tyrosine phosphatases (PTP) are important regulators of cellular signal transduction [1]. Several types of alterations of specific PTP functions have been reported in cancer cells, including gene deletion, allele loss, reduced expression by promoter methylation, or inactivation by point mutation or oxidation, all leading to loss
%K Acute myeloid leukemia
%K Protein-tyrosine phosphatases
%K Dual-specificity phosphatases (DUSP)
%K mRNA expression
%K Fms-like tyrosine kinase (FLT3) with internal tandem duplication (ITD)
%K DUSP6
%K ERK signaling
%U http://www.biosignaling.com/content/10/1/19