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A Preliminary Study On The Correlation Of Deletion Of Chronosome 13 And Gene P53 With Multiple Myeloma

Posted on:2011-12-01Degree:MasterType:Thesis
Country:ChinaCandidate:J T LiFull Text:PDF
GTID:2144360305967677Subject:Internal Medicine
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Objective:To compare the characteristics of fluorescein in sute hydrobride with G-band method in detecting genetics and cytogenetics of multiple myeloma; To investigate the incidence of 17p13 and/or del 13ql4 in patients with multiple myeloma and their correlation ship with clinical implication, treatment effects and survival duration.Method:Twenty two (male 12, female 10) new diagnosed multiple myeloma patients were investigated with median age of 66.3 (45-85) years old. There were 6 patients for IgA type,9 for IgG,5 for light chain,1 for IgD and 1 for non-secretary type; Nine of the 22 patients suffered with renal dysfunction. When classified according to the ISS clinical stage, there were 3 cases at Stage I,5 at stage II and 14 at Stage III. All the bone marrow samples were detected by G-band method, and metaphase FISH was used to detect the del 13ql4 (Rb1 gene) and del 17p13 (P53 gene). Meanwhile, the clinical characteristics of the patients were compared via t test, Kaplan-meier was applied to analize the survival duration, log-rank method was addressed to the odd ratio of the survival rate, and Fisher test were used to measure the detection difference between the FISH and G-band method and the relationship with the clinical efficacy accordingly.Results:Abnormal genetic detection rate: Eight of 22 patients (36.4%) were detected with 13q14 and 9 (40.9%) with del 17p13 via FISH method, with the total detection rate of abnormal genetics as 59.1% (13/22). Three of the 22 patients (13.6%) were found to have abnormal chromosome using G-band method, including-6,-8,-10,-12,-14,+14,+mar and t(9;22). It is shown that the detection rate of abnormal chromosome via FISH is higher than that of G-band, P=0.055。The clinical manifestation: There is no difference of demographic and disease characters between genetic deletion group and the normal ones, such as ages, gender, disease type, renal function, blood cell counting, LDH and serum calcium.Treatment effects:Thirteen patients with abnormal genes were treated with conventional chemotherapies with 3 cases achieving CR,4 cases VGPR,3 cases PR and 3 cases without response, whose total effective rate was 69.2% (9/13) and the mean survival duration 14.5 months. Nine patients with normal genes responded to the treatment with 2 cases acquiring CR,3 cases VGPR,3 cases PR and one without response. The total effective rate was added up to 88.8 (8/9) and survival duration prolonged to 45.4 months. The treatment response rate and survivl duration were both greater in patients with normal genetics than those with abnormal ones but there was no statistical significance between the groups, with p value of 0.29 and 0.41 respectively. The survival duration for patients with both genetic deletion (4 cases) and normal genes (9 cases) were 9.4 and 45.4 respectively, p=0.13.Among the 16 patients treated with conventional chemotherapies, the mean survival duration was 10.4 months and 43.9 months in patients with either genetic deletion and those without genetic deletion respectively,P=0.31; 9.3 months or 47.4 months in patients with or without P53 deletion with a prolonged survival duration for the latter group, P=0.08; The similar result was also seen in the patients with or without RBI deletion whose survival duration were 11.5 months and 41.6 months respectively, p=0.48.Treatment regimen effects on the response rate:4 of the 13 patients with genetic deletion were treated with Bortezomib,2 patients achieving CR,1 VGPR and 1 dead. The total effective rate (CR+VGPR) is up to 75%. Seven patients were treated with conventional chemotherapy acquiring the effective rate (CR+VGPR) as 27.6% with 2 VGPR,3 PR and 2 no response, p=0.19. The survival duration of the two treatment groups are 16 and 10.3 months with P value as 0.67.Conclusion:1. Either of Rbl and P53 genetic deletion was detected with much higher rate in multiple myeloma patients, which results in the shortened survival duration. Bearing with both abnormal genes will cause patients worse outcome. Patients at first diagnosis should be routine detected to select a proper therapy regimen.2. FISH was found with a much higher detection rate on genetic and cytogenetic abnormality in multiple myeloma patients. However, when to detect the complex chromosomal and unknown genetic abnormality, G-band method is more preferred. Combining both methods will bring about much more clinical significance. It's better to use grouping FISH in order to detect the complex genetic abnormality.3. The abnormal genetic rate was higher in patients at stage III than those at stage I, which implied that the cytogenetic abnormality might be an adverse factor on patients outcome. 4. Bortezomib may improve the prognosis of patients with genetic abnormalities。...
Keywords/Search Tags:multiple myeloma, cytogenetics, G band, FISH, bortezomib
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