title: TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance.
abstract: OBJECTIVE
  TEL gene rearrangements due to the 12;21 chromosomal translocation are the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a B-precursor immunophenotype. The limited number of clinically useful genetic markers in this leukemia subtype prompted us to assess TEL status as a predictor of treatment outcome.
  
  
  METHODS
  We determined the status of the TEL gene (rearranged or germline) in 188 cases of B-precursor acute leukemia using Southern blot analysis and related the findings to event-free survival. All comparisons of outcome were stratified by treatment regimen, risk classification, age, and leukocyte count.
  
  
  RESULTS
  Forty-eight patients (26%) had a rearranged TEL gene. At 5 years of follow-up, an estimated 91% +/- 5% (SE) of this group were event-free survivors, compared with only 65% +/- 5% of the group with germline TEL (stratified log-rank P = .011). For nonhyperdiploid patients, the odds ratio of an adverse event in the germline TEL group to that for the rearranged TEL group was 4.06 (95% confidence interval, 1.86 to 8.84). The relationship of TEL rearrangement to a favorable prognosis was independent of recognized good-risk features in B-precursor leukemia, including age, initial leukocyte count, and hyperdiploidy.
  
  
  CONCLUSIONS
  Rearrangement of the TEL gene distinguishes a large subset of children with favorable-prognosis B-precursor leukemia who cannot be identified by standard prognostic features. It may be possible to treat these patients less aggressively without loss of therapeutic efficacy.
authors.affiliation: Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: J R
authors.initials: JR
authors.lastname: Downing
authors.forename: C H
authors.initials: CH
authors.lastname: Pui
authors.forename: S A
authors.initials: SA
authors.lastname: Shurtleff
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: D R
authors.initials: DR
authors.lastname: Head
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: G K
authors.initials: GK
authors.lastname: Rivera
authors.forename: M L
authors.initials: ML
authors.lastname: Hancock
authors.forename: J M
authors.initials: JM
authors.lastname: Boyett
authors.forename: A
authors.initials: A
authors.lastname: Buijs
authors.forename: G
authors.initials: G
authors.lastname: Grosveld
authors.forename: F G
authors.initials: FG
authors.lastname: Behm
mesh_terms: D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D018572:Disease-Free Survival; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D005819:Genetic Markers; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein