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Although <jats:italic>STAT3<\/jats:italic> mutations are frequently detected in PRCA patients, the roles of other mutational profiles and their impact on clinical characteristics remain unclear. In this study, whole-exome sequencing and targeted sequencing using a custom-designed panel were performed on 53 PRCA patients. The most frequently mutated genes were <jats:italic>STAT3<\/jats:italic> (36%), <jats:italic>PCLO<\/jats:italic> (9%), <jats:italic>TET2<\/jats:italic> (9%), <jats:italic>NEB<\/jats:italic> (6%), <jats:italic>DNMT3A<\/jats:italic> (6%), and <jats:italic>POT1<\/jats:italic> (6%). Based on genetic profiles, patients were classified into three groups: those with <jats:italic>STAT3<\/jats:italic> variants (group S), those without <jats:italic>STAT3<\/jats:italic> variants but with variants in clonal hematopoiesis (CH)-related genes (group C), and those without variants in either <jats:italic>STAT3<\/jats:italic> or CH-related genes (group O). Patients in group C had a higher median age compared to group S, while group S exhibited milder anemia severity than group C. Additionally, <jats:italic>POT1<\/jats:italic> variants were associated with the idiopathic subtype of PRCA in females, often co-occurring with <jats:italic>STAT3<\/jats:italic> variants. Variants in CH-related genes and other genes, including <jats:italic>STAT3<\/jats:italic> and <jats:italic>POT1<\/jats:italic>, may play crucial roles in the pathophysiology of PRCA.<\/jats:p>","DOI":"10.1007\/s00277-025-06356-4","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:51:35Z","timestamp":1744170695000},"page":"1471-1479","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mutational heterogeneities in STAT3 and clonal hematopoiesis-related genes in acquired pure red cell aplasia"],"prefix":"10.1007","volume":"104","author":[{"given":"Toru","family":"Kawakami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiro","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Matsuzawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Yamane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuga","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ami","family":"Asakura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daigo","family":"Higano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Miyairi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoko","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Nishina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiro","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"issue":"21","key":"6356_CR1","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1182\/blood-2016-05-717140","volume":"128","author":"RT Means Jr","year":"2016","unstructured":"Means RT Jr (2016) Pure red cell aplasia. 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