Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study

J Clin Oncol. 2008 May 1;26(13):2186-91. doi: 10.1200/JCO.2007.14.3552.

Abstract

Purpose: To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL).

Patients and methods: TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years.

Results: Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (+/- SE) for patients with TEL rearrangements was 86% +/- 2%, compared with 72% +/- 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002).

Conclusion: We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow / pathology
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Gene Rearrangement*
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Sex Factors
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein