The downside to diversification

Role of V(D)J recombination in leukemogenesis

Dr. Dale Ramsden and colleagues at UNC-Chapel Hill report in the June 15th issue of G&D on the potential contribution of V(D)J recombination to genomic instability and cancer formation.

V(D)J recombination is the assembly of the immune system's mature antigen-specific receptor genes through the rearrangement of separate V, D and J components in developing B and T cells. The RAG1 and RAG2 recombinase enzymes catalyze the initial DNA binding and cleavage, and occasionally, the fragment excised during cleavage randomly integrates into the genome.

Dr. Ramsden and colleagues demonstrate that this aberrant recombination is not as rare as previously thought, and can generate the chromosomal abnormalities found in human lymphomas.

Using a novel and more biologically relevant experimental system, the scientists determined that in pre-B cells, about one out of every 50,000 V(D)J recombinations results in an unexpected, and potentially dangerous, transposition. The authors note that this frequency translates to roughly 10,000 transpositions per day for the average adult. Dr. Ramsden reasons that "Evolution tamed a transposon for our adaptive immune response: our results indicate its domestication is less complete than hoped."


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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