Analysis of mutagenic V(D)J recombinase mediated mutations at the HPRT locus as an in vivo model for studying rearrangements with leukemogenic potential in children

Pediatric acute lymphocytic leukemia (ALL) is a multifactorial malignancy with many distinctive developmentally specific features that include age specific acquisition of deletions, insertions and chromosomal translocations. The analysis of breakpoint regions involved in these leukemogenic genomic rearrangements has provided evidence that many are the consequence of V(D)J recombinase mediated events at both immune and non-immune loci. Hence, the direct investigation of in vivo genetic and epigenetic features in human peripheral lymphocytes is necessary to fully understand the mechanisms responsible for the specificity and frequency of these leukemogenic non-immune V(D)J recombinase events. In this review, I will present the utility of analyzing mutagenic V(D)J recombinase mediated genomic rearrangements at the HPRT locus in humans as an in vivo model system for understanding the mechanisms responsible for leukemogenic genetic alterations observed in children with leukemia.