Disruption of the RanBP17/Hox11L2 region by recombination with the TCRδ locus in acute lymphoblastic leukemias with t(5;14)(q34;q11)

The t(5;14)(g33-34;811) translocation constitutes a recurrent rearrangement in acute lymphoblastic leukemia involving the T cell receptor (TCR) δ locus on chromosome 14. Breakpoint sequences of the derivative chromosome 5 were isolated by application of a ligation-mediated PCR technique using TCR δ-specific primers to amplify genomic DNA from the leukemic cells of a patient with t(5;14). Through exon trap analysis, we identified various putative exons of the chromosome 5 target gene of the translocation; compilation of sequence information of trapped exons and available expressed sequence tags (ESTs) from the GenBank database allowed us to assemble 1.2 kb of the cDNA. Full-length cDNAs were isolated from a human testis cDNA library and sequence analysis predicted a putative Ran binding protein, a novel member of the importin-β superfamily of nuclear transport receptors, called RanBP1Z The t(5;14) breakpoint maps to the 3' coding region of the gene. The breakpoint of a second t(5;14) positive patient was mapped about 8 kb downstream of the most 3' RanBP17 exon and 2 kb upstream of the first exon of the orphan homeobox gene, Hox11L2. In both cases TCR δ enhancer sequences are juxtaposed downstream of the truncated or intact RanBP17 gene, respectively on the derivative chromosome. Leukemia (2002) 16, 2205-2212. doi:10.1038/sj.leu.2402671 Keywords: chromosomal translocation; acute lymphoblastic leukemia; RanBP17; Hox11 L2; T cell receptor δ