Abstract
Loss of the Y chromosome in bone marrow (BM) cells is a normal age‐associated event. Y chromosome loss is also observed in the Philadelphia chromosome (Ph) positive BM cells of some patients with chronic myeloid leukemia (CML) in chronic phase, but at a younger age than in normal individuals. While the significance of loss of the sex chromosome in normal males is uncertain, ‐Y marrow cells are not believed to be of clonal origin. However, because CML is a clonal disease, CML sub‐populations with Y loss may constitute a disease‐related sub‐clone. We used a PCR‐amplified yeast artificial chromosome containing the BCR gene region for single color interphase analysis of BCR rearrangement by fluorescence in situ hybridization (FISH). Then, using two color FISH, with one fluorochrome detecting the BCR gene region and the other detecting Y chromosome repeat sequences, we surveyed peripheral and BM Y loss in both normal Ph‐ (BCR not disrupted) and CML Ph+ (BCR rearranged) interphase nuclei of two patients with Y loss in Ph positive cells observed by metaphase analysis. ‐Y was seen in a proportion of Ph+ cells in both cases, and the proportion matched that seen in Ph‐ cells, indicating that Y loss is probably sporadic in both normal and CML populations, and that the propensity for Y loss in normal BM cells may be a phenotype that can be retained by malignant cells in CML.