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 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.
Jonsson
O G
OG
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Kitchens
R L
RL
Baer
R J
RJ
Buchanan
G R
GR
Smith
R G
RG
D000483:Alleles; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry; D002872:Chromosome Deletion; D015321:Gene Rearrangement; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic