V(D)J RECOMBINATION ACTIVITY IN HUMAN HEMATOPOIETIC-CELLS - CORRELATION WITH DEVELOPMENTAL STAGE AND GENOME STABILITY

V(D)J recombinase activity was measured in an array of human cell line s derived from hematopoietic malignancies representing various lineage s and developmental stages. The level of recombinase activity was foun d to vary over a 2000-fold range between different cell lines. Several myeloid cell lines were positive for V(D)J recombinase activity provi ding additional insight into the relationship between myeloid and lymp hoid differentiation. Despite high levels of V(D)J recombination in tw o human acute lymphoblastic leukemia cell lines, the cytogenetic karyo type has remained essentially constant over several years of continuou s cell culture. Silencing of recombination of chromosomal and minichro mosomal targets has been strongly correlated with the replication of C pG methylated DNA in murine cells. Here, in human cells, we show that human minichromosomes bearing V(D)J recombination signals are protecte d well over 100-fold from recombination if they are CpG methylated, pr oviding a rational basis for the karyotypic stability in cells with hi gh levels of V(D)J recombination activity.