The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the delta T-cell receptor with TCL3, a conserved and activated locus at 10q24.
We cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the delta T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint-derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer-spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by the introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia.
Zutter
M
M
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
Hockett
R D
RD
Roberts
C W
CW
McGuire
E A
EA
Bloomstone
J
J
Morton
C C
CC
Deaven
L L
LL
Crist
W M
WM
Carroll
A J
AJ
Korsmeyer
S J
SJ
D000483:Alleles; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D001483:Base Sequence; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000276:immunology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology
D015703:Antigens, CD; D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell