 Disruption of the RanBP17/Hox11L2 region by recombination with the TCR delta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11).
JWG Janssen, PhD
University Clinics of Heidelberg, Heidelberg, Baden Wuerttemberg Germany
The t(5;14) (q33-34;q11) translocation constitutes a recurrent rearrangement in acute lymphoblastic leukemia involving the T-cell receptor (TCR) delta locus on chromosome 14. Breakpoint sequences of the derivative chromosome 5 were isolated by ligation-mediated PCR using TCR delta -specific primers and genomic DNA from the leukemic cells of a patient with t(5;14). Through exon trap analysis, we isolated and characterized a novel gene at 5q34, and a close human homologue. The presence of an importin-beta N-terminal domain, their size of approximately 110 kD, their nuclear localization and the fact that the homologue was identical to a gene of a recently submitted RanGTP binding protein (Ran BP16), suggest that its protein is a novel member of the importin-beta superfamily of nuclear transport receptors and was therefore called RanBP17. The t(5;14) breakpoint maps to the 3 prime coding region of the RanBP17 gene. The breakpoint of a second t(5;14) positive patient was mapped about 8 kb downstream of the most 3 prime RanBP17 exon and 2 kb upstream of the first exon of the orphan homeobox gene, Hox11L2. In both cases TCR delta enhancer sequences are juxtaposed downstream of the truncated or intact RanBP17 gene, respectively on the derivative chromosome. Recent data of Bernard et al (Leukemia 2001) showed activation of the Hox11L2 gene in T-ALL patients harboring a t(5;14)(q35;q32). In these cases the breakpoints on chromosome 5 were also mapped in the RanBP17 gene. The loss of putative 5 prime regulatory sequences and transcriptional activation of the Hox11L2 gene may therefore remain an alternative possibility in leukemogenesis.
KEY WORDS:
chromosome aberration,
human chromosome 5,
acute lymphoblastic leukemia.
For more information, contact hans_janssen@ukl.uni-heidelberg.de
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.
This presentation received an honorable mention in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.
http://www.cancerprev.org/Journal/Issues/26/101/992/4210
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