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

Olafur G. Jonsson, Richard L. Kitchens, Richard J. Baer, George R. Buchanan, R. Graham Smith

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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 106 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 ∼ 30% of T-ALLs.

Original languageEnglish (US)
Pages (from-to)2029-2035
Number of pages7
JournalJournal of Clinical Investigation
Volume87
Issue number6
DOIs
StatePublished - Jun 1991

Keywords

  • Helix-loop-helix proteins
  • Minimal residual disease

ASJC Scopus subject areas

  • Medicine(all)

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