Deregulation of protein phosphatase expression in acute myeloid leukemia
- 476 Downloads
Acute myeloid leukemia (AML) is a highly malignant disease of myeloid cell line. AML is the most frequent adult leukemia with inadequate treatment possibility. The protein phosphatases are critical regulators of cell signaling, and deregulation of protein phosphatases always contribute to cell transformation. Although many studies established a relationship between protein phosphatases and leukemia, little is known about the role of this group of proteins in AML. To address this issue, we initially identified the complete catalog of human protein phosphatase genes and used this catalog to study deregulation of protein phosphatases in AML. Using mRNA expression data of AML patients, we show that 11 protein phosphatases are deregulated in AML within 174 protein phosphatases. The GO enrichment study suggests that these genes are involved in multiple biological processes other than protein de-phosphorylation. Expression of DUSP10, PTPRC, and PTPRE was significantly higher than average expression in AML, and a linear combination of DUSP10, MTMR11, PTPN4, and PTPRE expressions provides important information about disease subtypes. Our results provide an overview of protein phosphatase deregulation in AML.
KeywordsAcute myeloid leukemia AML Protein phosphatase Protein tyrosine phosphatase Protein serine/threonine phosphatase Dual specificity protein phosphatase
Conflict of interest
The authors declared no conflict of interest.
- 1.Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-235358.PubMedCrossRefGoogle Scholar
- 7.Godfrey R, Arora D, Bauer R, Stopp S, Muller JP, Heinrich T, et al. Cell transformation by FLT3 ITD in acute myeloid leukemia involves oxidative inactivation of the tumor suppressor protein-tyrosine phosphatase DEP-1/PTPRJ. Blood. 2012;119(19):4499–511. doi: 10.1182/blood-2011-02-336446.PubMedCrossRefGoogle Scholar
- 8.Arora D, Kothe S, van den Eijnden M, Hooft van Huijsduijnen R, Heidel F, Fischer T, et al. Expression of protein-tyrosine phosphatases in Acute Myeloid Leukemia cells: FLT3 ITD sustains high levels of DUSP6 expression. Cell Commun Signal CCS. 2012;10(1):19. doi: 10.1186/1478-811X-10-19.CrossRefGoogle Scholar
- 9.Kazi JU, Sun J, Phung B, Zadjali F, Flores-Morales A, Ronnstrand L. Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. J Biol Chem. 2012;287(43):36509–17. doi: 10.1074/jbc.M112.376111.PubMedCrossRefGoogle Scholar
- 19.Gutierrez NC, Lopez-Perez R, Hernandez JM, Isidro I, Gonzalez B, Delgado M, et al. Gene expression profile reveals deregulation of genes with relevant functions in the different subclasses of acute myeloid leukemia. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2005;19(3):402–9. doi: 10.1038/sj.leu.2403625.CrossRefGoogle Scholar
- 21.Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, et al. Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas. Oncol Rep. 2012;28(3):931–6. doi: 10.3892/or.2012.1862.PubMedGoogle Scholar