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The Investigation Of Mechanism On Abnormality Of Chromosome 21 And Malignant Hematological Disorders

Posted on:2004-08-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:L J ZhangFull Text:PDF
GTID:1104360092495827Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The imbalance of chromatin content in cells is the basic cause resulting in tumor. It shows the abnormal number and constitution of chromosome in cy-. togenetics and amplification deletion and base alteration of DNA fragment in molecular level. At present the materials indicate that the patients of leukemia have some non - random chromosomal aberration, and these chromosomal abnormalities are correlated to special clinical situations, morphology and immunology characters of leukemia. The molecular biologic characters of chromosomal aberration make clear that genes play an important role in the cellular proliferation and differentiation. Plenty of investigations showed that detections of chromosomal alterations on diagnosis,treatment, prognosis and minimal residual disease were very important predictive factor. Cytogenetical research of malignant hematological disordersis of important clinical significance.Conventional cytogenetics can only analysis chromosome in metaphase, but it's hard for conventional cytogenetics to research interphase nucleus,terminal cell and complex chromosomal constitution. There must be unknown chromosomal aberration or complex type of chromosome which can' t be detected with common methods, for low proliferative property, unsatisfactory interphrase mitotic phase, insufficient splitting phase with good manifest band, complex alteration of chromosomal karyotype or latent chromosomal alteration make its application restricted.Fluorescence in situ hybridization (FISH) is a new techniques developed on the base of combination of conventional cytogenetical, molecular biological and immunologic techniques. It utilizes non - radioactive materials to label nucleic acid probe and can do qualitative, quantitative and localizing research of special sequence of DNA on the chromosome and interphase nucleus. It can overcome the deficiency of conventional cytogenetics, avoid some shortcoming of radioactive in situ hybridization and play great advantages on the clone analysis of malignant hematopathy and gene location et al. Occurrence of FISH makes cytogenetics enter a colorful age.Complex chromosomal rearrangement called marker chromosome occurs to many malignant tumors. Conventional cytogenetics can't label origins of these marker chromosomes that are the key of malignant hematopathy episode. At present, reports on the correlated research of marker chromosome's origin are few. The chromosome twenty- first is the smallest one among 46 chromosomal karyotypes, and play a very important role in the episode mechanism of leukemia. Thus are the origins of some small marker chromosomes correlated to chromosome twenty - first.Duo to the above cause, this research made the patients of leukemia as the research objects and utilize many kinds of probes of DNA (probe of DNA with special site AtelomereN centromere probe with unusual a satellite, whole chromosome paining probe) to make hybridization on all kinds of complex sequence of DNA with molecular biological methods-FISH, whole chromosome painting, and discussed some special alterations, complex chromosomal rearrangement and origin of cytogenetics on the malignant hematopathy. We tried to detecte the mechanism of leukemia duo to possible latent oncogenes or anti-oncogene through the alterations of gene localization, amplification and deletion et al, and offered the theory bases to clinical early diagnosis,treatment, minimal residual disease and prognosis of leukemia.Materials and Methods1. Patients selectionThere were 52 patients with ALL (1995 - 2002), and every specimen was checked by conventional cytogenetics; 44 patients with pro- B cell type ALL, 7 patients with B cell type ALL, 1 patient with T cell type acute lym-phocytic leukemia. Thirty - nine cases had pedia - ALL (6 months to 14 months), among them 36 cases with pro - B cell type ALL and 3 cases with B cell type ALL. Twenty -five men and fourteen women. Thirteen patients had adult - ALL (15 years to 55 years) ; among them 8 patients had pro - B cell type ALL, 4 patients had B...
Keywords/Search Tags:Fluorescence in situ hybridization (FISH), acute leukemia (AL), myelodysplastic syndrome (MDS), chromosome rearrangement, marker chromosome
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