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The Research Of BRCA1 Expression And DNA Ploidy In Leukemia Patients

Posted on:2011-12-08Degree:MasterType:Thesis
Country:ChinaCandidate:C X MaoFull Text:PDF
GTID:2154360308974248Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objesctive: To investigate the expression and significance of BRCA1 in leukemia and DNA index and DNA ploidy of the bone marrow cells, and to find their relationship with clinical prognosis so as to guide clinical diagnosis and treatment.Methods:1 Objects: Bone marrow samples from 85 patients with acute leukemia (AL), 20 patients with chronic myeloid leukemia (CML), and 15 normal controls were analyzed.2 Fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate the expression of BRCA1 in AL, CML. The statistical analysis were performed to evaluate the effect of BRCA1 expression values.3 DNA index and DNA ploidy of bone marrow cells in AL were studied by flow cytometry analysis (FCM),and their relationship with the expression of BRCA1 were analyzed.Results:1 Expression of BRCA1 in every groups1.1 Expression of BRCA1 in patients with acute myelogenous leukemia(AML)1.1.1 Expression of BRCA1 mRNA in patients with denovo and relapsed. 49 denovo AML patients were evaluated for BRCA1 mRNA expression, 23 were reduced, with a reduced rate of 46.9%. 15 normal controls were evaluated for BRCA1 mRNA expression, 2 were reduced, the rest were higher, with a reduced rate of 13.3%. The mRNA expression of BRCA1in denovo patients with AML was lower than that in normal control, with statistical significance(P<0.05). 7 patients with relapsed AML were evaluated for BRCA1mRNA expression, all patients were reduced, with a reduced rate of 100.0%. The mRNA expression of BRCA1in patients with relapsed AML was lower than that in denovo AML patients without statistical significance(P >0.05)and lower than that in normal control with statistical significance(P<0.05).1.1.2 Expression of BRCA1mRNA in AML patients who had achieved complete remission (CR)38 AML patients in CR were evaluated for BRCA1 mRNA expression, 7 patients were reduced, with a reduced rate of 18.4%. The mRNA level of BRCA1 in AML patients in CR was higher compared with denovo and relapsed AML patients, both with statistical significance (P<0.05), but lower compared with normal control without statistical significance(P >0.05). 11 AML patients in continuous complete remission (CCR) were evaluated for BRCA1mRNA expression, 2 were reduced, with a reduced rate of 18.1%. The mRNA level of BRCA1 both in AML patients in CR for less than 3 years and in AML patients in CCR were higher than that in denovo and relapsed AML patients, both with statistical significance(P<0.05)and lower than that in normal control without statistical significance(P >0.05). The mRNA level of BRCA1in AML patients in CR for less than 3 years was lower compared with CCR patients , but without statistical significance(P >0.05)1.2 Expression of BRCA1mRNA in patients with acute lymphoblastic leukemia(ALL)13 denovo ALL patients were evaluated for BRCA1 mRNA expression, 6 were reduced, with a reduced rate of 46.1%. The mRNA expression of BRCA1in denovo patients with ALL was lower than that in normal control, with statistical significanc(eP<0.05). 9 ALL patients in CR were evaluated for BRCA1mRNA expression, 3 were reduced, with a reduced rate of 33.3%. The mRNA level of BRCA1 in ALL patients in CR was higher compared with denovo ALL patients, with statistical significance (P<0.05), but lower compared with normal control without statistical significance(P >0.05). 5 patients with relapsed ALL were evaluated for BRCA1mRNA expression, all patients were reduced, with a reduced rate of 100.0%. The mRNA expression of BRCA1in patients with relapsed ALL was lower than that in denovo ALL patients without statistical significanc(eP >0.05)and lower than that in normal control with statistical significance(P<0.05).1.3 Expression of BRCA1mRNA in patients with chronic myeloid leukemia4 out of 20 patients with CML-CP were reduced for BRCA1 mRNA expression, with a reduced rate of 20%. The mRNA expression of BRCA1 in CML-CP was lower than that in normal control without statistical significance(P >0.05).2 The relationship between the expression of BRCA1 and therapeutic efficacy in acute leukemia patientsThe therapeutic efficacy in 58 of 62 denovo acute leukemia patients was evaluated (2 patient died early, 2patients gave up treatment). 47 of 58 AL patients achieved complete hematological response (CR) after induction therapy, with a CR rate of 81%(47/58). 38 of 47 acute myelogenous lecukemia(AML) patients achieved complete hematological response (CR) after induction therapy ,the mRNA level of BRCA1 in patient who have achieved CR was higher than that before treatment , and relapsed patients, both with statistical significance(P<0.05),but lower compared with normal control and CCR patients without statistical significance(P >0.05). 6 out of 9 patients of AML have not achieved complete hematological response (CR) after induction therapy were reduced for BRCA1mRNA expression, with a reduced rate of 66.7%. The mRNA level of BRCA1 in patient who have not achieved CR was higher than that before treatment, and relapsed patients, both without statistical significance (P >0.05),but lower in comparison with normal control and CCR patients with statistical significance(P<0.05).9 of 11 in acute lymphoblastic leukemia(ALL) patients achieved complete hematological response (CR) after induction therapy, the mRNA level of BRCA1 in patient who have achieved CR was higher than that before treatment , and relapsed patients, both with statistical significance(P<0.05),but lower compared with normal control without statistical significance(P >0.05).3 The result of DNA index and DNA ploidy in bone marrow cells of ALpatients DNA index and DNA aneuploid in denovo acute leukemia patients were lower than those in relapsed group without statistical significance(P>0.05).DNA index and DNA aneuploid in CR patients were lower than those in relapsed and denovo groups with statistical significance(P<0.05). DNA index and DNA aneuploid in patients achieving CR were lower than those in patients failing to achieve CR with statistical significance(P<0.05).The relationship of DNA aneuploid and The mRNA expression of BRCA1 in acute leukemia patients was analysed, without evident relevance.Conclusions:1 The mRNA expression of BRCA1 in denovo acute myelogenous leukemia was significantly lower than that in normal control. The mRNA level of BRCA1 in recurrent patients was lower than normal control and denovo acute myelogenous leukemia ,but without statistical significance in comparison with denovo acute myelogenous leukemia.The mRNA level of BRCA1 in CR patients with acute myelogenous leukemia was higher than that in patients with denovo or relapsed AML,but without significantly difference in comparison with normal control. The mRNA level of BRCA1 in patients with acute myelogenous leukemia who had been CR for less than 3 years didn't differ from that in AML patients with CCR .The mRNA level of BRCA1 in patients who have achieved CR was higher than that before treatment . The mRNA level of BRCA1 in patients who have not achieved CR was higher than that before treatment and relapsed patients without statistical significance and lower than that in CR patients and normal control with statistical significance. Suggesting that BRCA1 gene may be involved in the pathogenesis and progression of acute myelogenous leukemia. BRCA1 expression may be up-regulated following remission of leukemia and down-regulated following relapse. 2 The mRNA expression of BRCA1 in denovo acute lymphoblastic leukemia was significantly lower than that in normal control. The mRNA level of BRCA1 in recurrent patients was lower than normal control and denovo acute lymphoblastic leukemia ,but without statistical significance in comparison with denovo acute lymphoblastic leukemia.The mRNA level of BRCA1 in CR patients with acute myelogenous leukemia was higher than that in patients with denovo or relapsed ALL,but without significantly difference in comparison with normal control.The mRNA level of BRCA1 in patients who have achieved CR was higher than that before treatment . There were only 2 patients who have not achieved CR,so we didn't do statistical analysis.Suggesting that BRCA1 gene may be involved in the pathogenesis and progression of acute myelogenous leukemia. BRCA1 expression may be up-regulated following remission of leukemia and down-regulated following relapse.3 The mRNA expression of BRCA1 in patients with CML-CP was lower compared with normal control without statistical significance and was higher than that in both denovo and relapsed patients with acute myelogenous leukemia with statistical significance.4 DNA index and DNA aneuploid in denovo acute leukemia patients were lower than those in relapsed group without statistical significance. DNA index and DNA aneuploid in CR patients were lower than those in relapsed and denovo groups with statistical significance. DNA index and DNA aneuploid in patients achieving CR were lower than those in patients failing to achieve CR with statistical significance. Examining the acute leukemia patient's DNA index and the DNA aneuploid is helpful to understand patient's condition , so as to instruct the clinical diagnosis and treatment, and have vital practical significance to judge the prognosis .5 The expression of BRCA1 in AL wasn't in relation with DNA aneuploid.
Keywords/Search Tags:leukemia, breast cancer susceptibility gene 1, expression, fluorescent quantitative RT-PCR, DNA ploidy, FCM
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