Phosphatase Sequencing of Pediatric Acute Myeloid Leukemia Reveals a Novel Mutation in the Phosphatase Gene PTPN4

J Cloos, DGJ Cucchi, M Irandoust, Yehuda G. Assaraf, GJL Kaspers, M. Akyuz, A.J.F. Broekhuizen, N. Heijmans, Erik R. Abels, J Parigger, ZJ Kwidama, T.K. van den Berg, V de Haas, Dirk Reinhardt, Marry M van den Heuvel-Eibrink, E.S.J.M. De Bont, C.M. Zwaan, Edwin Cuppen, Ewart de Bruijn

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It has been well established that dysregulated activation of kinases is essential for the development of acute myeloid leukemia(AML). In contrast, little is known about the role of their dephosphorylation counterparts, the tyrosine phosphatases. Here we performed whole tyrosine phosphatome sequencing in 15 pediatric AML samples and found a somatic P394L mutation in the FERM-adjacent region of PTPN4. In the absence of a crystal structure of PTPN4, bioinformatics analysis with the software tool PROVEAN (Protein Variation Effect Analyzer) revealed that this P394L mutation is expected to inflict a deleterious effect on the phosphatase activity of PTNP4. Exploring the frequency of this PTPN4 mutation in 227 acute leukemia samples uncovered an additional silent A364A mutation in exon 13 of PTPN4. No additional mutations were found, which further emphasizes the low mutation burden in pediatric AML. Further functional studies are warranted to explore the actual impact of this P394L mutation on the structure and/or function of PTPN4.
Original languageEnglish
Article numberDOI: 10.31083/j.jmcm.2018.01.001
Pages (from-to)1-6
Number of pages6
JournalJournal of Molecular and Clinical Medicine
Issue number1
Publication statusPublished - 6 Nov 2017


  • Phosphatases; PTPN4 mutation; Acute Myeloid Leukemia

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