Scholarlink

<p><i>USP7</i> alterations in pediatric T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) remains incompletely understood. We investigated the clinical features and long-term outcomes associated with <i>USP7</i> mutations in a cohort of 313 pediatric T-ALL/LBL patients. <i>USP7</i> and <i>NOTCH1</i> mutations were detected by Sanger sequencing and their association with prognosis were analyzed. Cox regression and nomogram models were used to evaluate prognostic importance. We identified 12 patients with <i>USP7</i> heterozygous mutations (10 T-ALL, 2 T-LBL) with older age and higher proportion of not remission at day 15 morphological evaluation. Patients with <i>USP7</i> mutation showed significantly worse event-free survival (EFS) and overall survival (OS) compared to wild-type cases, both in T-ALL and combined T-ALL/LBL cohorts. Concurrent analysis of <i>USP7</i> and <i>NOTCH1</i> mutations revealed <i>USP7</i><sup><i>mut</i></sup><i>NOTCH1</i><sup><i>wt</i></sup> genotype was associated with the worst, whereas <i>USP7</i><sup><i>wt</i></sup><i>NOTCH1</i><sup><i>mut</i></sup> was linked to the best EFS and OS in both T-ALL and T-ALL/LBL groups. <i>USP7</i> mutation, pre-consolidation MRD ≥ 10<sup>−4</sup> and CNS leukemia were independent adverse factors for EFS, and the former two were also predictors for OS. <i>USP7</i> mutation status was validated as the most influential prognostic factor, with prediction models including <i>USP7</i> status showing enhanced accuracy. In conclusion, <i>USP7</i> mutations define a subset of T-ALL/LBL patients with adverse outcomes on conventional intensive treatment.</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

USP7 mutations are associated with adverse outcomes in pediatric T cell acute lymphoblastic leukemia and lymphoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月22日

查看全文
  • Jun Li,
  • Yuan Yuan,
  • Feng-Feng Niu,
  • Ying Wang,
  • Wei Lin,
  • Rui-Dong Zhang,
  • Ling Jin,
  • Yan-Long Duan,
  • Chao Gao

摘要

USP7 alterations in pediatric T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) remains incompletely understood. We investigated the clinical features and long-term outcomes associated with USP7 mutations in a cohort of 313 pediatric T-ALL/LBL patients. USP7 and NOTCH1 mutations were detected by Sanger sequencing and their association with prognosis were analyzed. Cox regression and nomogram models were used to evaluate prognostic importance. We identified 12 patients with USP7 heterozygous mutations (10 T-ALL, 2 T-LBL) with older age and higher proportion of not remission at day 15 morphological evaluation. Patients with USP7 mutation showed significantly worse event-free survival (EFS) and overall survival (OS) compared to wild-type cases, both in T-ALL and combined T-ALL/LBL cohorts. Concurrent analysis of USP7 and NOTCH1 mutations revealed USP7mutNOTCH1wt genotype was associated with the worst, whereas USP7wtNOTCH1mut was linked to the best EFS and OS in both T-ALL and T-ALL/LBL groups. USP7 mutation, pre-consolidation MRD ≥ 10−4 and CNS leukemia were independent adverse factors for EFS, and the former two were also predictors for OS. USP7 mutation status was validated as the most influential prognostic factor, with prediction models including USP7 status showing enhanced accuracy. In conclusion, USP7 mutations define a subset of T-ALL/LBL patients with adverse outcomes on conventional intensive treatment.