Molecular analysis of a t(11;14)(q23;q11) from a patient with null-cell acute lymphoblastic leukemia

✍ Scribed by Robert C. Burnett; Rafael Espinosa III; Thomas B. Shows; Roger L. Eddy; Michelle M. Lebeau; Janet D. Rowley; Dr. Manuel O. Diaz

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 764 KB
• Volume: 7
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870070107

✦ Synopsis

Ip;&-3qChromosome I I, 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( I 1;14)(q23;ql I). The chromosome 14 breakpoints occurred within the TCRD locus, close t o two diversity segments. The chromosome I I 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 TCRAID locus on the normal chromosome 14 had undergone a V62-D63-$Ja joining. Two phage clones with this VDJ rearrangement were isolated; one of these contained an intra-]a region deletion. Two clones with the derivative I I junction were isolated; one of these had a similar, but not identical, deletion. A heptamer-nonarner recognition sequence (located -70 kb 5' t o Ca), not associated with a TCR gene coding segment, was found in the immediate vicinity of both 5' breakpoints. We have designated this sequence 5'de' for 5' deleting element. An intra-Jcx region deletion involving this heptamer-nonarner was previously identified in the leukemia cells recovered from a patient who had T-cell ALL. Fifty kilobases of DNA on I I q23 surrounding the breakpoint were cloned and analyzed. No CpG islands or conserved sequences were identified within this region. Fluorescence in situ hybridization analysis showed that this I I q23 breakpoint mapped distal t o the MLL gene associated with the recurring breakpoints in the 4; I I, 9; I I, and I I ; I9 translocations, distal t o the RCK gene associated with an I I ; I 4 translocation, and proximal t o the ETS I gene, which is located at I lq24.