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TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood
acute lymphoblastic leukemia
TW McLean, S Ringold, D Neuberg, K Stegmaier, R Tantravahi, J Ritz, HP Koeffler, S Takeuchi, JW Janssen, T Seriu, CR Bartram, SE Sallan, DG Gilliland and TR Golub
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard
Medical School, Boston, MA, USA.
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.
Volume 88,
Issue 11,
pp. 4252-4258,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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J. Biol. Chem.,
March 16, 2001;
276(12):
9421 - 9436.
[Abstract]
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F. Salomon-Nguyen, V. Della-Valle, M. Mauchauffe, M. Busson-Le Coniat, J. Ghysdael, R. Berger, and O. A. Bernard
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion
PNAS,
June 6, 2000;
97(12):
6757 - 6762.
[Abstract]
[Full Text]
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