Figure 7.

Proximity effects. (A) Schematically shows 1 chromosome 9 (dark blue) and 1 chromosome 22 (red) in an interphase cell nucleus. Locations of the ABL and BCR genes are indicated by arrows; centromeres by contractions. If 2 DNA double-strand breaks occur, one in each of the 2 genes, and the breaks come close together spatially, misrepair can induce the translocation shown schematically in panel B. The translocation makes a BCR-ABL oncogene (too small to be visible at this scale) located at the color junction shown, that is, can turn a LSC-predecessor cell into a CML LSC. By modeling the BCR-ABL translocation frequency based on the sizes of the relevant introns of BCR and ABL, and comparing the resulting probability with CML incidence, it is possible to estimate the number of LSC-predecessor cells at risk, independently for radiation-induced and age-induced translocations. Experimental data show that in normal individuals, the 2 loci are on average closer together than randomness would indicate, implying a higher BCR-ABL translocation probability and thus a lower estimate of the number of LSC-predecessor cells needed to explain observed CML incidence.