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 Citations (Scopus)

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
StatePublished - Jun 1991

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Alleles
Genes
Gene Rearrangement
Chromosomes, Human, Pair 1
Therapeutics
Genome
DNA

Keywords

  • Helix-loop-helix proteins
  • Minimal residual disease

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia. / Jonsson, Olafur G.; Kitchens, Richard L.; Baer, Richard J.; Buchanan, George R.; Smith, R. Graham.

In: Journal of Clinical Investigation, Vol. 87, No. 6, 06.1991, p. 2029-2035.

Research output: Contribution to journalArticle

Jonsson, Olafur G. ; Kitchens, Richard L. ; Baer, Richard J. ; Buchanan, George R. ; Smith, R. Graham. / Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 6. pp. 2029-2035.
@article{0bc75d6b1eea4193a996ebd050c118ab,
title = "Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia",
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.",
keywords = "Helix-loop-helix proteins, Minimal residual disease",
author = "Jonsson, {Olafur G.} and Kitchens, {Richard L.} and Baer, {Richard J.} and Buchanan, {George R.} and Smith, {R. Graham}",
year = "1991",
month = "6",
language = "English (US)",
volume = "87",
pages = "2029--2035",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia

AU - Jonsson, Olafur G.

AU - Kitchens, Richard L.

AU - Baer, Richard J.

AU - Buchanan, George R.

AU - Smith, R. Graham

PY - 1991/6

Y1 - 1991/6

N2 - 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.

AB - 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.

KW - Helix-loop-helix proteins

KW - Minimal residual disease

UR - http://www.scopus.com/inward/record.url?scp=0026042304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026042304&partnerID=8YFLogxK

M3 - Article

C2 - 2040693

AN - SCOPUS:0026042304

VL - 87

SP - 2029

EP - 2035

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -