Juxtaposition of the T-cell receptor alpha-chain locus (14q11) and a region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia.
We describe a t(14;14)(q11;q32) translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia (AT). By using a battery of joining (J)-segment probes from the T-cell receptor (TCR) alpha-chain locus TCRA, three distinct J alpha rearrangements were observed. One rearrangement reflected a normal TCRA variable (V) region V alpha-to-J alpha recombination. The second rearrangement was caused by the translocation even itself, which joined a DNA segment from 14q32 centromeric to the immunoglobulin heavy chain locus (IGH) and a J alpha gene located approximately 75 kilobases (kb) 5' of the TCRA constant region gene (C alpha). A third rearrangement involved a 17-kb internal deletion 3' to the translocation, a rearrangement within the J alpha locus that has been observed once before in a patient with AT. Analysis of these three rearrangements underscores the increase in aberrant locus-specific recombination in lymphocytes from patients with AT. Furthermore, these studies support the view that a growth-effecting gene is present in the 14q32 region that participates in the leukemogenic process.
Davey
M P
MP
Metabolism Branch, National Institutes of Health, Bethesda, MD 20892.
Bertness
V
V
Nakahara
K
K
Johnson
J P
JP
McBride
O W
OW
Waldmann
T A
TA
Kirsch
I R
IR
D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D015139:Blotting, Southern; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D005796:Genes; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015458:Leukemia, T-Cell / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014178:Translocation, Genetic
D011948:Receptors, Antigen, T-Cell