Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia

Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic...

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Bibliographic Details
Published in:The Journal of clinical investigation 1991-06, Vol.87 (6), p.2029-2035
Main Authors: JONSSON, O. G, KITCHENS, R. L, BAER, R. J, BUCHANAN, G. R, SMITH, R. G
Format: Article
Language:English
Subjects:
Alleles
Base Sequence
Biological and medical sciences
Bone Marrow - chemistry
Chromosome Deletion
Gene Rearrangement
Hematologic and hematopoietic diseases
Humans
Leukemia-Lymphoma, Adult T-Cell - diagnosis
Leukemia-Lymphoma, Adult T-Cell - genetics
Medical sciences
Molecular Sequence Data
Nucleic Acid Hybridization
Polymerase Chain Reaction
Translocation, Genetic
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Summary:Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemias contain clustered rearrangements of the tal-1 locus. To test whether these rearrangements can serve as markers for residual disease, we monitored four patients with T-ALL; three of the leukemias contained a deleted (tald) and one a translocated (talt) tal-1 allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood of one patient during the 4th mo of treatment but not thereafter. Using a quantitative assay to measure the fraction of tald alleles in DNA extracts, we estimated that this month 4 sample contained 150 tald copies per 10(6) genome copies. The patient with t(1;14)(p34;q11) (talt) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in complete remission 11-20 mo into treatment. We conclude that tal-1 rearrangements provide useful clonal markers for approximately 30% of T-ALLs.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI115232