Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia
Language English Country Germany Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
9341866
DOI
10.1007/s004390050547
Knihovny.cz E-resources
- MeSH
- Fusion Proteins, bcr-abl genetics MeSH
- Cell Nucleus chemistry MeSH
- Bone Marrow Cells MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics MeSH
- DNA, Neoplasm analysis MeSH
- DNA Probes genetics MeSH
- Adult MeSH
- Philadelphia Chromosome MeSH
- Genes, abl genetics MeSH
- In Situ Hybridization, Fluorescence methods MeSH
- Interphase MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphocytes radiation effects MeSH
- Image Processing, Computer-Assisted methods MeSH
- Proto-Oncogene Proteins c-bcr MeSH
- Proto-Oncogene Proteins genetics MeSH
- Proto-Oncogenes genetics MeSH
- Protein-Tyrosine Kinases * MeSH
- Gamma Rays MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- BCR protein, human MeSH Browser
- Fusion Proteins, bcr-abl MeSH
- DNA, Neoplasm MeSH
- DNA Probes MeSH
- Proto-Oncogene Proteins c-bcr MeSH
- Proto-Oncogene Proteins MeSH
- Protein-Tyrosine Kinases * MeSH
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 microns 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 gamma-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 micron 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 micron) 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.
References provided by Crossref.org
Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change