title: Case-control study suggests a favorable impact of TEL rearrangement in patients with B-lineage acute lymphoblastic leukemia treated with antimetabolite-based therapy: a Pediatric Oncology Group study.
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.
authors.affiliation: St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: V J
authors.initials: VJ
authors.lastname: Land
authors.forename: M P
authors.initials: MP
authors.lastname: Link
authors.forename: D J
authors.initials: DJ
authors.lastname: Pullen
authors.forename: B M
authors.initials: BM
authors.lastname: Camitta
authors.forename: C H
authors.initials: CH
authors.lastname: Pui
authors.forename: J R
authors.initials: JR
authors.lastname: Downing
authors.forename: F G
authors.initials: FG
authors.lastname: Behm
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics*; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D002648:Child; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit; D003561:Cytarabine / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016037:Single-Blind Method; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000964:Antimetabolites, Antineoplastic; D001215:Asparaginase; D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D003561:Cytarabine; D004273:DNA, Neoplasm; D006854:Hydrocortisone; D015122:Mercaptopurine; D008727:Methotrexate; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011241:Prednisone; D014750:Vincristine; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein