title: TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia.
abstract: Polymerase chain reaction-based screening of childhood acute lymphoblastic leukemia (ALL) samples showed that a TEL/AML1 fusion transcript was detected in 27% of all cases, representing the most common known gene rearrangement in childhood cancer. The TEL/AML1 fusion results from a t(12;21)(p13;q22) chromosomal translocation, but was undetectable at the routine cytogenetic level. TEL/AML1-positive patients had exclusively B-lineage ALL, and most patients were between the ages of 2 and 9 years at diagnosis. Only 3/89 (3.4%) adult ALL patients were TEL/AML1-positive. Most importantly, TEL/AML1-positive children had a significantly lower rate of relapse compared with TEL/AML1-negative patients (0/22 v 16/54, P = .004). Co-immunoprecipitation experiments demonstrated that TEL/AML-1 formed homodimers in vitro, and heterodimerized with the normal TEL protein when the two proteins were expressed together. The elucidation of the precise mechanism of transformation by TEL/AML1 and the role of TEL/AML1 testing in the treatment of childhood ALL will require additional studies.
authors.affiliation: Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: McLean
authors.forename: S
authors.initials: S
authors.lastname: Ringold
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: K
authors.initials: K
authors.lastname: Stegmaier
authors.forename: R
authors.initials: R
authors.lastname: Tantravahi
authors.forename: J
authors.initials: J
authors.lastname: Ritz
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: J W
authors.initials: JW
authors.lastname: Janssen
authors.forename: T
authors.initials: T
authors.lastname: Seriu
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: S E
authors.initials: SE
authors.lastname: Sallan
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
authors.forename: T R
authors.initials: TR
authors.lastname: Golub
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics* / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000648:ultrastructure; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000235:genetics; D019281:Dimerization; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D015993:Life Tables; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011519:Proto-Oncogenes; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein