Predominance of Fetal Type DJ. Joining in Young Children with B Precursor Lymphoblastic Leukemia as Evidence for an In Utero Transforming Event

The presence of N sequences in the complementarity determining region 3 (CDR3) of the rearranged immunoglobulin H chain is developmentally regulated: N regions are generally present in the DJH joinings of adult B cells but are often absent in fetal B cells. Analysis of the CDK3 in 61 B precursor acute lymphoblastic leukemias indicated that 87.5% of the leukemias obtained from children ~3 yr old lacked N regions at the DJH junction. In contrast, in children >3 yr old, only 11.1% of the leukemias lacked N regions at this junction, a frequency similar to what we have observed in B cells from children and adults. These findings suggest that the majority of leukemias presenting within the first 3 yr of age arise from an in utero transforming event.