Molecular analysis of the t(1;19) breakpoint cluster region in pre-b cell acute lymphoblastic leukemias

✍ Scribed by Julia O. Mellentin; Jamison Nourse; Stephen P. Hunger; Stephen D. Smith; Dr. Michael L. Cleary

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 699 KB
• Volume: 2
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870020313

✦ Synopsis

The t( I; 19) chromosomal translocation in acute lymphoblastic pre-B cell leukemias involves the gene €2A for helix-loop-helix (HLH) proteins E I2 and E47, ubiquitous transcriptional proteins implicated in the regulation of various lymphoid and nonlymphoid genes. To characterize the molecular features of the t( I ; I9)(q23;p I 3) translocation, we molecularly cloned breakpoint DNA from t ( I ; I9)-carrying pre-B cell leukemias. In all cases, breakpoints on chromosome I 9 occurred within 2 kb of each other in a single intron of the €3 gene. This clustered arrangement resulted in specific truncation of the €2 gene and transcript, with loss of sequences encoding the basic DNA-binding and HLH dimerization motifs from the derivative I 9 chromosome. In contrast, breakpoints on chromosome I were distributed over a large region and could not be linked t o exonic sequences of the PBXl gene, although identical chromosome I sequences are joined t o E2A sequences in I ; 19 fusion transcripts. These data show that the I ; I 9 translocation consistently results in exchange of 3' exons encoding the HLH motifs of €24 with DNA from chromosome 1 t o form a fusion gene on the derivative I 9 chromosome.