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.
Publication types
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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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Adolescent
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Adult
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biomarkers, Tumor* / chemistry
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Child
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Child, Preschool
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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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Cloning, Molecular
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Core Binding Factor Alpha 2 Subunit
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DNA, Neoplasm / genetics
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Dimerization
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Female
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Gene Deletion
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Humans
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Infant
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Life Tables
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Male
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Neoplasm Proteins / analysis
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Neoplasm Proteins / chemistry*
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Neoplasm Proteins / genetics
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Oncogene Proteins, Fusion*
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Polymerase Chain Reaction
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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Prognosis
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Proto-Oncogenes
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Survival Analysis
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Translocation, Genetic*
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Treatment Outcome
Substances
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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