Genetic basis for iMCD-TAFRO.

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^P128L mutation and a germline RUNX1^G60C mutation in two patients with iMCD-TAFRO, respectively. The MEK2^P128L 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^G60C mutation aboli

SUBMITTER: Yoshimi A 

PROVIDER: S-EPMC7148173 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature