Molecular analysis of a t(11;14)(q23;q11) from a patient with null-cell acute lymphoblastic leukemia.
/lp;&-3qChromosome 11, band q23, is the frequent site of recurring cytogenetic rearrangements in human leukemia. We have cloned and sequenced the breakpoint junctions from a patient who had null-cell acute lymphoblastic leukemia (ALL) with a t(11;14)(q23;q11). The chromosome 14 breakpoints occurred within the TCRD locus, close to two diversity segments. The chromosome 11 breakpoint occurred between two head-to-head heptamer sequences, and junctional diversity was evident at both derivative junctions, suggesting involvement of the V(D)J recombinase. The TCRA/D locus on the normal chromosome 14 had undergone a V delta 2-D delta 3-psi J alpha joining. Two phage clones with this VDJ rearrangement were isolated; one of these contained an intra-J alpha region deletion. Two clones with the derivative 11 junction were isolated; one of these had a similar, but not identical, deletion. A heptamer-nonamer recognition sequence (located approximately 70 kb 5' to C alpha), not associated with a TCR gene coding segment, was found in the immediate vicinity of both 5' breakpoints. We have designated this sequence 5'del for 5' deleting element. An intra-J alpha region deletion involving this heptamer-nonamer was previously identified in the leukemia cells recovered from a patient who had T-cell ALL. Fifty kilobases of DNA on 11q23 surrounding the breakpoint were cloned and analyzed. No CpG islands or conserved sequences were identified within this region.(ABSTRACT TRUNCATED AT 250 WORDS)
Burnett
R C
RC
Department of Medicine, University of Chicago, IL 60637.
Espinosa
R
R
Shows
T B
TB
Eddy
R L
RL
LeBeau
M M
MM
Rowley
J D
JD
Diaz
M O
MO
D000328:Adult; D001483:Base Sequence; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000097:blood / Q000302:isolation & purification; D015246:Deoxyribonuclease EcoRI; D005260:Female; D015723:Gene Library; D015321:Gene Rearrangement; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D015183:Restriction Mapping; D017384:Sequence Deletion; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D007133:Immunoglobulin Joining Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015246:Deoxyribonuclease EcoRI