Abstract
TEL gene rearrangement is the most common genetic lesion in pediatric acute lymphoblastic leukemia (ALL), occurring in about 25% of B-lineage cases. We previously showed that, among patients treated on St Jude protocols, TEL rearrangement independently conferred an excellent prognosis. To extend these results to patients treated with antimetabolite-based therapy, we performed Southern blot analysis to determine the TEL gene status of 104 cases of B-lineage ALL treated on Pediatric Oncology Group 8602, matched on age, gender, and leukocyte count. There were 52 failures among the 77 patients with germline TEL, compared with only 8 failures among 27 patients in the rearranged group. Based on a two-sided logistic regression analysis, stratified for age (subdivided at 10 years), leukocyte count (subdivided at 50,000), and gender, the estimated odds of failing by 4 years in the germline TEL group is 5.4 times that of the rearranged TEL group, with 95% confidence from 1.9 to 15.6, two-sided P = .0009. Thus, the presence of a rearranged TEL gene is also associated with an improved survival among patients treated with antimetabolite-based therapy. Our results indicate that all newly diagnosed ALL patients should be screened for TEL gene rearrangements and suggest that these patients are candidates for less intensive therapy.
Publication types
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Clinical Trial
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Controlled Clinical Trial
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Multicenter Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antimetabolites, Antineoplastic / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Asparaginase / administration & dosage
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Biomarkers, Tumor / genetics*
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Blotting, Southern
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Burkitt Lymphoma / drug therapy*
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / mortality
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Case-Control Studies
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Child
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Chromosomes, Human, Pair 12 / genetics
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Chromosomes, Human, Pair 12 / ultrastructure
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Chromosomes, Human, Pair 21 / genetics
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Chromosomes, Human, Pair 21 / ultrastructure
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Core Binding Factor Alpha 2 Subunit
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Cytarabine / administration & dosage
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DNA, Neoplasm / genetics*
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Female
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Humans
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Hydrocortisone / administration & dosage
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Male
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Mercaptopurine / administration & dosage
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Methotrexate / administration & dosage
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Neoplasm Proteins / genetics*
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Oncogene Proteins, Fusion*
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Prednisone / administration & dosage
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Prognosis
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Remission Induction
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Retrospective Studies
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Single-Blind Method
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Translocation, Genetic
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Treatment Outcome
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Vincristine / administration & dosage
Substances
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Antimetabolites, Antineoplastic
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Biomarkers, Tumor
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Core Binding Factor Alpha 2 Subunit
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DNA, Neoplasm
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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TEL-AML1 fusion protein
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Cytarabine
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Vincristine
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Mercaptopurine
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Asparaginase
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Prednisone
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Hydrocortisone
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Methotrexate