| The Study of Topology of genetic material relative tochronic myeloid leukemia in interphase nucleousThe study to neoplasm morbility mechanism is heat subject at all time in medical territory. But most of the studies have been focused on variations of the genes relative to tumor, meanwhile, the relativity between topologic changes of genetic material in the nuclear spaces and the tumor genesis and evolution has not been pay much attention. In the end of 70's, a presumption has been raised that each chromatin occupies a territory in the nucleus, which being called chromatin territory. Many mathematics model have been submitted to explain the relationship between chromatin topologic structure and its function. Most people believe that chromatin territory locations in nucleus are constant, and exhibit regular changes in cell cycle. In the genesis of tumor, a series of variations of the chromatin territory topology, including volume, surface area and the location in nuleus space, may take place. The familiar chromosome translocations in tumor are correlate to their conformation in nucleus. Adjacent chromosomes translocation are more frequent than non-adjacent chromosomes, that means chromosome locations in the space of nucleus determine the frequency of translocation and tumor genesis.Chronic myeloid leukemia (CML) is a hematopoietic therioma deriving from a singleness clone, ph chromosome, existing in 95% CML, is formed by reciprocal translocation of chromosome 9 and 22. c-abl gene in the long arm of chromosome 9 and break point concentration region (BCR) in the long arm of chromosome 22 translocate and form bcr-abl fusion gene, which code p210fusion protein having tyrosine kinase activity and; is a key in CML genesis. In clinical, CML has been divided into chronic period, acceleration period and blast period. Each period has distinct heterogenicity, and, .extra variations of chromosomes and genes emerge in bla$t period. But we still do not know if these variations are related to the changes of chuomatin topology in nucleus, and what kind of rules of these variations in CMLigenesis and evolution.Conbined with flurescence in situ hybridization (FISH) and confoeal laser scanning microscope (CLSM), we observed the topologic characters of genetic material relative to CML using single copy sequence bcr, c-abl, c-myc and p53 DNA probes, chromosome 8, 9, 17 and 22 whole chromosome probe(WCP). The results show that all genes are distributed non-randomly in 3-dimension space of interphase nucleus of IM-9, human lymphocyte cell line, and K562 cell line. The fusion of bcr and abl genes are consistent with their distribution in the same ugion which prompts that the fusion frequency of genes are positive correlate to their relative 3-dimension location' in the interphasenucleus. Homogenous chromatin exhibit diversities in topologic characters and dynamic changes in cell cycle. Chromatin condensation and decondensation have a intimate relationship with its activity, and homologous chromatin exist differences in chromatin condensation degree. Irradiation may facilitate approximability of bcr and abl genes in the nucleus of IM-9 cell, alter the figure and condensation of chromosome 9 and chromosome 22, making them more extent and active. These results could explain irradiation can lead to the fusion of bci and abl genes.CML is a kind of malignancy clone proliferation disease. Almost all cases will lead to blast. When the occurrence of blast, c-myc and p53 genes location in the interphase of nucleus may change obviously. They movetoward to the nuclear center at blast period. Meanwhile, the topology of chromosome 8 and chromosome 17 vary dramatically and be more approximating to K562 cell. These results hint that the location variation of c-myc and p53 genes in nuclear space and the topologic changes of chromosome 8 and chromosome 17 are relative to CML blast. The variation of these genes and chomatin could be indicator to estimate CML blast.
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