{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yoshimi A"],"funding":["MEXT | Japan Society for the Promotion of Science","Castleman Awareness and Research Effort/Castleman Disease Collaborative Network","Starr Foundation","Lauri Strauss Leukemia Foundation","NHLBI NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute","Pershing Square Foundation","NCI NIH HHS","Edward P. Evans Foundation","Leukemia and Lymphoma Society"],"pagination":["3218-3225"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7148173"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(15)"],"pubmed_abstract":["TAFRO syndrome, a clinical subtype of idiopathic multicentric Castleman disease (iMCD), consists of a constellation of symptoms/signs including thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly. The etiology of iMCD-TAFRO and the basis for cytokine hypersecretion commonly seen in iMCD-TAFRO patients has not been elucidated. Here, we identified a somatic MEK2<sup>P128L</sup> mutation and a germline RUNX1<sup>G60C</sup> mutation in two patients with iMCD-TAFRO, respectively. The MEK2<sup>P128L</sup> mutation, which has been identified previously in solid tumor and histiocytosis patients, caused hyperactivated MAP kinase signaling, conferred IL-3 hypersensitivity and sensitized the cells to various MEK inhibitors. The RUNX1<sup>G60C</sup> mutation aboli"],"journal":["Oncogene"],"pubmed_title":["Genetic basis for iMCD-TAFRO."],"pmcid":["PMC7148173"],"funding_grant_id":["I8-A8-075","P30 CA008748","R01 HL128239"],"pubmed_authors":["Trippett TM","Dogan A","Baik J","Zhang N","Fajgenbaum DC","Xiao W","Penson AV","Harada H","Arcila ME","Yoshimi A","Pichardo J","Chen X","Sigler A","Abdel-Wahab O"],"additional_accession":[]},"is_claimable":false,"name":"Genetic basis for iMCD-TAFRO.","description":"TAFRO syndrome, a clinical subtype of idiopathic multicentric Castleman disease (iMCD), consists of a constellation of symptoms/signs including thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly. The etiology of iMCD-TAFRO and the basis for cytokine hypersecretion commonly seen in iMCD-TAFRO patients has not been elucidated. Here, we identified a somatic MEK2<sup>P128L</sup> mutation and a germline RUNX1<sup>G60C</sup> mutation in two patients with iMCD-TAFRO, respectively. The MEK2<sup>P128L</sup> mutation, which has been identified previously in solid tumor and histiocytosis patients, caused hyperactivated MAP kinase signaling, conferred IL-3 hypersensitivity and sensitized the cells to various MEK inhibitors. The RUNX1<sup>G60C</sup> mutation aboli","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Apr","modification":"2026-05-01T01:00:55.321Z","creation":"2020-08-15T07:09:17Z"},"accession":"S-EPMC7148173","cross_references":{"pubmed":["32051554"],"doi":["10.1038/s41388-020-1204-9"]}}