LOCALIZATION AND DISTANCE BETWEEN ABL AND BCR GENES IN INTERPHASE NUCLEI OF BONE-MARROW CELLS OF CONTROL DONORS AND PATIENTS WITH CHRONIC MYELOID-LEUKEMIA

Quantitative measurements of the nuclear localisation of the ABL and B CR genes and the distance between them were performed in randomly orie nted bone marrow cells of control donors and patients with chronic mye loid leukaemia (CML). Most ABL and BCR genes (75%) are located at a di stance of 20-65% of the local radius from the nuclear centre to the nu clear membrane. A chimeric BCR-ABL gene located on a derivative chromo some 22 resulting from t(9;22)(q34;q11) [the so-called Philadelphia (P h) chromosome] as well as the intact ABL and BCR genes of patients suf fering from chronic myeloid leukaemia are also located mostly in this region, which has a mean thickness of 2 mu m in bone marrow cells. We have not found any significant differences in the location of the two genes in the G(1) and G(2) phases of the cell cycle, nor between bone marrow cells and stimulated lymphocytes. Irradiation of lymphocytes wi th a dose of 5 Gy of gamma-rays results in a shift of both genes to th e central region of the nucleus (0-20% of the radius distant from the nuclear centre) in about 15% of the cells. The minimum distance betwee n one ABL and one BCR gene is less than 1 mu m in 47.5% of bone marrow cells of control donors. Such a small distance is found between homol ogous ABL and between homologous BCR genes in only 8.1% and 8.4% of ce lls, respectively. It is possible that the relative closeness of nonho mologous ABL and BCR genes in interphase nuclei of bone marrow cells c ould facilitate translocation between these genes. In 16.4% of bone ma rrow cells one ABL and one BCR gene are juxtaposed (the distance betwe en them varies from 0-0.5 mu m) and simulate the Ph chromosome. This j uxtaposition is the result of the projection of two genes located one above another into a plane, as follows from the probability calculatio n.