Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
OBJECTIVE
To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL).


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).


CONCLUSIONS
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.
Rubnitz
Jeffrey E
JE
Department of Oncology, Mail Stop 260, St Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105-2794, USA. jeffrey.rubnitz@stjude.org
Wichlan
David
D
Devidas
Meenakshi
M
Shuster
Jonathan
J
Linda
Stephen B
SB
Kurtzberg
Joanne
J
Bell
Beverly
B
Hunger
Stephen P
SP
Chauvenet
Allen
A
Pui
Ching-Hon
CH
Camitta
Bruce
B
Pullen
Jeanette
J
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein