Scholarlink

<p>Dysregulation of T cell-mediated immunity is considered a major pathophysiological mechanism in acquired pure red cell aplasia (PRCA), including idiopathic PRCA, large granular lymphocytic leukemia-associated PRCA, and thymoma-associated PRCA. Although <i>STAT3</i> 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 <i>STAT3</i> (36%), <i>PCLO</i> (9%), <i>TET2</i> (9%), <i>NEB</i> (6%), <i>DNMT3A</i> (6%), and <i>POT1</i> (6%). Based on genetic profiles, patients were classified into three groups: those with <i>STAT3</i> variants (group S), those without <i>STAT3</i> variants but with variants in clonal hematopoiesis (CH)-related genes (group C), and those without variants in either <i>STAT3</i> 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, <i>POT1</i> variants were associated with the idiopathic subtype of PRCA in females, often co-occurring with <i>STAT3</i> variants. Variants in CH-related genes and other genes, including <i>STAT3</i> and <i>POT1</i>, may play crucial roles in the pathophysiology of PRCA.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mutational heterogeneities in STAT3 and clonal hematopoiesis-related genes in acquired pure red cell aplasia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月1日

查看全文
  • Toru Kawakami,
  • Fumihiro Kawakami,
  • Shuji Matsuzawa,
  • Taku Yamane,
  • Yuga Mizuno,
  • Ami Asakura,
  • Daigo Higano,
  • Shotaro Miyairi,
  • Kaoko Sakai,
  • Sayaka Nishina,
  • Hitoshi Sakai,
  • Yasushi Kubota,
  • Yumiko Higuchi,
  • Hideyuki Nakazawa,
  • Fumihiro Ishida

摘要

Dysregulation of T cell-mediated immunity is considered a major pathophysiological mechanism in acquired pure red cell aplasia (PRCA), including idiopathic PRCA, large granular lymphocytic leukemia-associated PRCA, and thymoma-associated PRCA. Although STAT3 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 STAT3 (36%), PCLO (9%), TET2 (9%), NEB (6%), DNMT3A (6%), and POT1 (6%). Based on genetic profiles, patients were classified into three groups: those with STAT3 variants (group S), those without STAT3 variants but with variants in clonal hematopoiesis (CH)-related genes (group C), and those without variants in either STAT3 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, POT1 variants were associated with the idiopathic subtype of PRCA in females, often co-occurring with STAT3 variants. Variants in CH-related genes and other genes, including STAT3 and POT1, may play crucial roles in the pathophysiology of PRCA.