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-specificDNA rearrangements in leukemiclympho-blasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(l;14Xp34;q1l)translocation associated withT cell acute lym-phoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-i 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-) 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 (tal) tal-i allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood ofone 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 tall copies per 106 genome copies. The patient with t(1;14Xp34;q11) (tat) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in com-plete remission 11-20 mo into treatment. We conclude that tal-i rearrangements provide useful clonal markers for- 30% of T-ALLs. (J. Clin. Invest. 1991. 87:2029-2035.) Key words: minimal residual disease * helix-loop-helix protein