The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Abstract

We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.

Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha.

“…Often dysregulated expression of these genes seems to lead to cell transformation. One of these genes, identified by analysis of the (1;14)(p34;qll) translocation in '-3% of patients with T cell acute lymphocytic leukemia (T-ALL), is tal-i (Begley et al, 1989;Finger et al, 1989;Bernard et al, 1990;Carroll et al, 1990;Chen et al, 1990a). The same gene was also found to be expressed in the 'stem cell' leukemia blast crisis of chronic myelogenous leukemia, where it was termed SCL (Begley et al, 1989).…”

“…Aberrant expression of TAL-] occurs in most patients with T-ALL (Bash et al, 1995). Although inter-chromosomal translocations involving TAL-] are relatively rare (Begley et al, 1989;Finger et al, 1989;Bernard et al, 1990;Carroll et al, 1990;Chen et al, 1990b), activation of TAL-I can occur by two other mechanisms. Twenty five percent of patients undergo a precise interstitial 90 kb deletion of a portion of the 5' region of chromosome 1 which brings the promoter of a T cell-specific gene of unknown function, termed SIL (SCL/TAL-interrupting locus), into proximity with TAL-], resulting in expression of TAL-] in the T cell (Aplan et al, 1990;Brown et al, 1990).…”

The translocation (1;14)(p34;q11) in human t‐cell leukemia: Chromosome breakage 25 kilobase pairs downstream of the tal1 protooncogene

“…However, the (1;14)(p34;qll) translocation was detected in bone marrow cells obtained at relapse, as illustrated in Figure 2. Since this was the sixth observation of t(1;14)(p34;qll) in the Pediatric Oncology Group (POG) 8600 classification study of ALL (Carroll et al, 1990), the patient will be referred to as case number 6.…”

“…About 25 percent of T-ALL patients exhibit a nearly precise 90 kilobase pair (kbp) deletion (designated TALd) of the upstream sequence from one allele of the TALl locus (Brown et al, 1990;Jonsson et al, 1991); the TALd deletion results from a site-specific DNA rearrangement that presumably represents aberrant activity of the immunoglobulin recombinase (Brown et al, 1990;Aplan et al, 199Ob). An additional 3% of T-ALL patients harbor t(1;14)(p34;qll), a chromosome translocation that transposes TALl from its normal location on chromosome 1 into the T-cell receptor (TCR) a/& chain complex on chromosome 14 (Begley et al, 1989Finger et al, 1989Bernard et al, 1990Carroll et al, 1990;Chen et al, 199Oa, b). Since structural lesions of TALl are commonly and exclusively associated with T-ALL, TALl gene alteration is likely to be a critical factor in T-cell leukemogenesis.…”

“…The arrows indicate the approximate position of the breakpoints on the derivative (der) chromosomes. Details of the cytogenetic methodology have been previously described(Carroll et al, 1990).…”