title: Incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia.
abstract: The TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most common gene rearrangement in childhood leukemia, occurring in approximately 25% of pediatric acute lymphoblastic leukemia (ALL), and is associated with a favorable prognosis. For example, a cohort of pediatric patients with ALL retrospectively analyzed for the TEL/AML1 fusion treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols between 1980 to 1991 demonstrated a 100% relapse-free survival in TEL/AML1-positive patients with a median of 8.3 years of follow-up. However, two recent studies analyzing pediatric patients with relapsed ALL have reported the same incidence of the TEL/AML1 rearrangement as in patients with newly diagnosed ALL, suggesting that TEL/AML1 positivity is not a favorable prognostic indicator. To clarify this apparent discrepancy, 48 pediatric patients treated on Dana-Farber Cancer Institute (DFCI) protocols with ALL at first or second relapse were tested for TEL/AML1 using reverse transcriptase-polymerase chain reaction (RT-PCR). The TEL/AML1 fusion was identified in only 1 of 32 analyzable relapsed ALL patients, in concordance with our previous reports of improved disease-free survival in TEL/AML1-positive patients. The low frequency of TEL/AML1-positive patients at relapse is significantly different than that reported in other studies. Although there are several potential explanations for the observed differences in TEL/AML1-positive patients at relapse, it is plausible that relapse-free survival in TEL/AML1-positive patients may be changed with different therapeutic approaches. Taken together, these results support the need for prospective analysis of prognosis in TEL/AML1-positive patients.
authors.affiliation: Division of Hematology-Oncology, Brigham and Women's Hospital, Department of Pediatric Oncology the Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Loh
authors.forename: L B
authors.initials: LB
authors.lastname: Silverman
authors.forename: M L
authors.initials: ML
authors.lastname: Young
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: T R
authors.initials: TR
authors.lastname: Golub
authors.forename: S E
authors.initials: SE
authors.lastname: Sallan
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D018572:Disease-Free Survival; D005787:Gene Frequency / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein