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Study on Correlation between Early Diagnosis and Prognosis of Malignant Blood Diseases and Micronucleus Expression

Author: WangRunChao
Tutor: BaiOu
School: Jilin University
Course: Internal Medicine
Keywords: Micronucleus leukemia myelodysplastic syndrome early diagnosis prognosis
CLC: R55
Type: Master's thesis
Year: 2011
Downloads: 34
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Abstract

Objectives:Micronucleus is located in cytoplasm independent of the nucleosome core. Micronucleus formation is highly relevant to chromosome break, deletion, and aberrations, micronucleus detection can reflect chromosome damage indirectly. Micronucleus test can reflect chromosome damage that caused by environmental mutagens, carcinogens and other harmful agents. Some studies at home and abroad show that micronucleus expression is relevant with early diagnosis and prognosis of some malignant blood diseases,such as acute leukemia and myelodysplastic syndrome. It appears before the cancer,even more earlier than symptom and sign. Micronucleus can be used as a symbol of cancer at an early stage, patients who have more micronucleus expression have poor prognosis and treatment effects.based on the above,the study is aimed to explore correlation between early diagnosis and prognosis of malignant blood diseases and micronucleus expression.Method:1.We detected micronucleus expression of peripheral blood lymphocytes from clinical cases in the past year,which included different groups:acute leukemia,myelodysplastic syndrome, malignant solid tumors and benign blood diseases(all cases are initial for diagnosis and treatment).and put health person as control,observed the difference among different groups.2.We analysised correlation between micronucleus expression and age in different groups.And analysised differences of micronucleus expression between male and female in different groups.3.We analysised differences of MNF and MNCF among four MDS subtypes(include RCUD,RCMD,RAEB-1,RAEB-2), and analysised the relations between micronucleus expressions and karyotype.we followed up some MDS cases,and detected micronucleus dynamically,to observe the correlation between prognosis and micronucleus expression.4.We analysised relations between micronucleus rate and some early prognostic indicators of acute leukemia patients.5.We used K562 and NB4 cell lines.Cell growth was observed by inverted phase microscope. Cells were seeded in 96-well plates at a density of 100,000 per well.Cells were incubated with various concentrations of cytarabine.Each experimental condition was done in sextuplicate and repeated at least twice. Cell viability was measured at 24h,48h and 72h after we added cytarabine by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl etrazolium bromide (MTT) assay.Meanwhile we observed micronucleus expression of the cell lines.Then analysised relations between micronucleus expression and cell growth inhibition ratio.Results:1.There had no significant difference between malignant solid tumor and acute leukemia, which were significantly higher than that of MDS, MDS group was significantly higher than benign blood diseases,which were ignificantly higher than that of normal control group.2.Micronucleus expression of normal control group and malignant solid tumors group had a significant positive correlation with age, the correlation was weak in other groups;There had no significance between micronucleus expression and gender in those groups except normal control group,in which micronucleus expression of male was significant higher than female, there had no significant difference in other groups.3.In MDS group, there had no significant difference between RCUD and RCMD, the same result was also showed between RAEB-1 and RAEB-2, but the latter two groups was significantly higher than the former two groups.4.In MDS patients, There is a correlation between the karyotype abnormal rate and micronucleus rate.5.We observed 4 cases of MDS patients continuously,2 of which with stable disease had stable micronucleus expression. The other 2 cases had disease progressed ultimately, the micronucleus rate increased gradually.6. There has no significant difference between ALL group and AML group.The micronucleus frequency of leukemia patients had correlation with curative effect, high expression of micronucleus indicate poor prognosis.7.We seeded K562 and NB4 cell lines in vitro, its micronucleus frequency and cell growth inhibition rate increased with growth of drug concentration and acting time.Conclusions:1.Micronucleus express differently in the normal control group and groups of different diseases, malignant solid tumors and leukemia group were the highest.2. Micronucleus express differently in different subtypes of MDS; Aynamic monitoring of micronucleus expression rate can reflect progress of MDS.Micronucleus expression have positive correlation with the karyotype abnormal rate,and it can reflect abnormal situation of genetic material.3.There has no significant difference between ALL group and AML group,high expression of micronucleus indicate poor prognosis.4. The micronucleus frequency and cell growth inhibition rate of K562 and NB4 cell lines increased with growth of drug concentration and acting time.

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