Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia |
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Authors: | Emílie Luká?ová Stanislav Kozubek Michal Kozubek Jana Kjeronská Leonard Rýznar Jana Horáková Eva Krahulcová Gerda Horneck |
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Institution: | (1) Institute of Biophysics, AS CR, Královopolská 135, CZ-612 65 Brno, Czech Republic Tel.: +42-5-41-51-71-39; Fax: +42-5-41-24-04-98,;(2) Department of Engineering Science, Oxford University, OX1 3PJ, Oxford, UK, GB;(3) Haematological Clinic of Faculty Hospital, Brno, Czech Republic,;(4) Deutsche Forschungsanstalt für Luft- und Raumfahrt, Institut für Luft- und Raumfahrtmedizin, Cologne, Germany, DE |
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Abstract: | Quantitative measurements of the nuclear localisation of the ABL and BCR genes and the distance between them were performed
in randomly oriented bone marrow cells of control donors and patients with chronic myeloid leukaemia (CML). Most ABL and BCR
genes (75%) are located at a distance of 20–65% of the local radius from the nuclear centre to the nuclear membrane. A chimeric
BCR-ABL gene located on a derivative chromosome 22 resulting from t(9;22)(q34;q11) the so-called Philadelphia (Ph) chromosome]
as well as the intact ABL and BCR genes of patients suffering from chronic myeloid leukaemia are also located mostly in this
region, which has a mean thickness of 2 μm in bone marrow cells. We have not found any significant differences in the location
of the two genes in the G1 and G2 phases of the cell cycle, nor between bone marrow cells and stimulated lymphocytes. Irradiation of lymphocytes with a dose
of 5 Gy of γ-rays results in a shift of both genes to the central region of the nucleus (0–20% of the radius distant from
the nuclear centre) in about 15% of the cells. The minimum distance between one ABL and one BCR gene is less than 1 μm in
47.5% of bone marrow cells of control donors. Such a small distance is found between homologous ABL and between homologous
BCR genes in only 8.1% and 8.4% of cells, respectively. It is possible that the relative closeness of nonhomologous ABL and
BCR genes in interphase nuclei of bone marrow cells could facilitate translocation between these genes. In 16.4% of bone marrow
cells one ABL and one BCR gene are juxtaposed (the distance between them varies from 0–0.5 μm) and simulate the Ph chromosome.
This juxtaposition is the result of the projection of two genes located one above another into a plane, as follows from the
probability calculation.
Received: 5 September 1996 / Accepted: 15 April 1997 |
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