{"doi":"10.31083/j.jmcm.2018.01.001","title":"Phosphatase Sequencing of Pediatric Acute Myeloid Leukemia Reveals a Novel Mutation in the Phosphatase Gene PTPN4","abstract":"<jats:p>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.</jats:p>","journal":"Journal of Molecular and Clinical Medicine","year":2018,"id":637061,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1653908,"name":"Mahban Irandoust","orcid":null,"position":1,"is_corresponding":false},{"id":363231,"name":"Yehuda G. Assaraf","orcid":"0000-0001-6692-8221","position":2,"is_corresponding":false},{"id":1653909,"name":"Gertjan JL Kaspers","orcid":null,"position":3,"is_corresponding":false},{"id":1653910,"name":"Ewart de Bruijn","orcid":null,"position":4,"is_corresponding":false},{"id":1653911,"name":"Mercan Akyuz","orcid":null,"position":5,"is_corresponding":false},{"id":1653913,"name":"Richard AJF Broekhuizen","orcid":null,"position":6,"is_corresponding":false},{"id":1653915,"name":"Nika Heijmans","orcid":null,"position":7,"is_corresponding":false},{"id":1653916,"name":"Erik R Abels","orcid":null,"position":8,"is_corresponding":false},{"id":1653918,"name":"Josta Parigger","orcid":null,"position":9,"is_corresponding":false},{"id":1653920,"name":"Zinia Kwidama","orcid":null,"position":10,"is_corresponding":false},{"id":1653922,"name":"Timo K van den Berg","orcid":null,"position":11,"is_corresponding":false},{"id":1653923,"name":"Valérie de Haas","orcid":null,"position":12,"is_corresponding":false},{"id":1370729,"name":"Dirk Reinhardt","orcid":"0000-0002-7027-4483","position":13,"is_corresponding":false},{"id":1653924,"name":"Marry M van den Heuvel-Eibrink","orcid":null,"position":14,"is_corresponding":false},{"id":1653925,"name":"Eveline SJM de Bont","orcid":null,"position":15,"is_corresponding":false},{"id":1653926,"name":"C Michel Zwaan","orcid":null,"position":16,"is_corresponding":false},{"id":48139,"name":"Edwin Cuppen","orcid":"0000-0002-0400-9542","position":17,"is_corresponding":false},{"id":462151,"name":"Jacqueline Cloos","orcid":"0000-0001-9150-8026","position":18,"is_corresponding":false},{"id":1653907,"name":"David GJ Cucchi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phosphatase Sequencing of Pediatric Acute Myeloid Leukemia Reveals a Novel Mutation in the Phosphatase Gene PTPN4","abstract":"<jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W2916662452","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.11681953,"influential_citations":0,"citation_trend":[{"year":2025,"count":1}],"oa_status":"gold","license":null,"oa_locations":[{"url":"https://jmcm.imrpress.org/EN/article/downloadArticleFile.do?attachType=PDF&id=32","host_type":"journal"},{"url":"https://jmcm.imrpress.org/EN/article/downloadArticleFile.do?attachType=PDF&id=32","host_type":"publisher"},{"url":"https://www.imrpress.com/journal/JMCM/1/1/10.31083/j.jmcm.2018.01.001","host_type":"publisher"},{"url":"https://doi.org/10.31083/j.jmcm.2018.01.001","host_type":"journal"}],"fields_of_study":["Protein Tyrosine Phosphatases","ATP Synthase and ATPases Research"],"mesh_terms":[],"keywords":["Mutation","PTPN11","Myeloid leukemia","Biology","Exon","Protein tyrosine phosphatase","Dephosphorylation","Phosphatase","Cancer research","Missense mutation","Genetics","Somatic cell","Gene","Phosphorylation","Molecular biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T18:13:37.244373Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}