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)