The Clinical and Molecular Characterization of Distinct Subtypes in Adult T Cell Acute Lymphoblastic Leukemia

Cancer Sci. 2025 Apr;116(4):1126-1138. doi: 10.1111/cas.70010. Epub 2025 Feb 7.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal proliferative malignant disease characterized by abnormal T-cell development. The classification of T-ALL primarily hinges on immunophenotype, encompassing early T-cell precursor (ETP)-ALL, near-ETP-ALL, and non-ETP-ALL. We summarized clinical information from 117 patients, with genetic data available for 77 patients and transcriptomic data available for 24 patients. An ETP-like score model was established based on transcriptome, aiming to address the subjectivity in the current T-ALL immunophenotype classification. The retrospective analysis indicated that ETP immunophenotype was not a prognostic factor for T-ALL patients. Compared to non-ETP-ALL patients, ETP-like patients including ETP-ALL and near-ETP-ALL were more likely to carry MED12 gene mutations, which may predict a dismal outcome. Transcriptomic analysis suggested that T-ALL patients with different immunophenotypes were in accordance with the T-cell development trajectory, while ETP-like patients exhibited characteristics of early T-cell development. Finally, we established an ETP-like score model and confirmed its efficiency across four independent cohorts, with sensitivity exceeding 80%. And T-ALL patients with high ETP-like score were associated with poor prognosis. In conclusion, our study elucidated the clinical and molecular features of distinct subtypes of T-ALL patients, providing new valuable insights for T-ALL classification.

Keywords: T‐cell acute lymphoblastic leukemia; classification; early T‐cell precursor acute lymphoblastic leukemia; genetic abnormality; transcriptome.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Mutation
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / classification
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Prognosis
  • Retrospective Studies
  • Transcriptome
  • Young Adult