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Analysis of Genetic Changes in Chronic Myeloid Leukemia

Author: RanDongMei
Tutor: LiuYanFang
School: Zhengzhou University
Course: Internal Medicine
Keywords: CML FISH BCR / ABL fusion gene
CLC: R733.7
Type: Master's thesis
Year: 2009
Downloads: 28
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Abstract


Background and purposeChronic myeloid leukemia(CML) is a clonal malignant disease of hematopoietic stem cellPhiladelphia chromosome(Philadelphia,Ph) is found in 90%-95%CML patients,which is a translocation part of chromosome 9(q 34) with that of chromosome 22(q 11),resulting in t(9;22)(q 34;q 11).Translocation(9;22)(q 34;q 11) induces the formation of new chimeric gene bcr/abl fusion gene P210 bcr/abl gene expression of the fusion protein enhances the tyrosine kinase activity,through a variety of signal transduction,interfered with normal hematopoietic procedures,such as proliferation,adhesion and apoptosis of myeloid cells,eventually leading to malignant cell proliferation of CML.As early as 1960s,the Ph chromosome was found in patients with CMLCML is a hematopoietic stem cell disease in a high degree of heterogeneity with Ph chromosome as specific chromosomal abnormalities,In particular,at the initial phase of access to patients with CML,Ph chromosome contribute to the diagnosis and treatment of CML.Statistics shown that 90%-95%of CML patients with Ph chromosome,a few of patients had complex chromosomal abnormalitie.About 5%of CML may have variations of Ph or complex chromosome karyotype changes,especially in accelerated phase and blast crisis.Did not receive special treatment in patients with CML in general 2 to 3 years experience of the chronic phase,in the transformation process,the genetic test can be found in patients with additional chromosomal abnormalities,these abnormalities often appear in the Prior to clinical change and become malignant clone the main mechanism for progress. At present,all of the fusion genes in leukemia has not yet been fully established.Bone marrow karyotype analysis is necessary. Karyotype analysis of CML exerts monitoring and prognostic significance in the diagnosis and treatment of CML.Conventional karyotype analysishave been some studied andreported in recent years,but on the combination of it with the use of molecular biology method-fluorescence in situ by bridization(FISH)and PCR are open to explore.Karyotype analysis of 194 cases of CML patients was performed in this study.The abnormalities of genetics and molecular geneticsand its roles in the diagnosis and treatment of CML were discussed.1.Materials and Methods1.1 Research subjects Patients with CML in 194 cases,who were hospitalized in First Affiliated Hospital of Zhengzhou University during January 2005 -through June 2009 were studied.Out of 194 cases,128 cases of male,female 66 cases(male to female ratio is about 2:1),aged 7~75 years old(average age 38 years).Diagnosis and staging of CML is based on clinical performance,blood,bone marrow and neutrophil alkaline phosphatase and in the light of results such as "blood disease diagnosis and efficacy standards" in regard to the diagnosis of CML phases standards determined.Clinical stages:chronic phase(CP) 146 cases,Accelerated phase(AP) and blast crisis phase(BC) 48 cases.1.2.Methods1.2.1 Conventional cytogenetics(cc):Chromosome analysis of bone marrow cells from patients,the use of short-term training prepared 24h bone marrow chromosomes, the application of G-banding karyotype analysis carried out.1.2.2 Fluorescence in situ hybridization(FISH) technology is the conventional cytogenetic method based on the use of molecular biology methods-fluorescence in situ hybridization(FISH) technology,the use of a number of site-specific DNA probes(chromosome-wide pollution and special sites,two-color fusion probe ectopic) for karyotype analysis.1.3.X~2 test used to conduct statistical analysis 2.Results2.1.194 cases of CML patients,Ph chromosome-positive(Ph +) 166 cases(85.57%), of which 133 cases of chronic phase,33 cases of accelerated phase and BC.152 cases (91.56%) has a typical chromosomal translocation t(9:22)(q34:q11).14 cases(8.4%) had variant translocations,including eight cases of complex translocation,six cases of a simple translocation.28 cases were Ph chromosome-negative(Ph~-),with 13 cases of chronic phase,15 cases of accelerated phase and BC,2.2.28 cases of Ph~-patients,13 patients were found in other chromosome abnormalities.Major chromosomal aberrations,including-21(5 cases),-7-17(1 case), -17+22(3 cases),+8(4 cases).166 cases of ph~+ CML patients,28/166 patients (16.86%),accompanied by additional chromosomal abnormalities.Which three cases of patients with chronic phase system,the main type of dual-ph~+ +8 17q+;Department 25 cases of CML patients,CML patients accounted for 75.6%of the total,the extra chromosome abnormalities,including -22(6 cases),-21 cases(4 cases),-11(3 cases), +8(2 cases),-10(2 cases),+14(1 case),+20(1 case),9q+(1 case),21+(1 case), 19p+(1 cases),17q+(1),15q+(1 cases),17q(1 case).This shows that most common chronic myelogenous followed by an additional chromosome abnormalities as the main as follows:-22,-21,-11,+8,-10,and +14 and so on.20 cases of coexistence of two abnormal clones,of which 19 cases of CML,1 case of chronic phase.6 cases had three abnormal clones,including 1 case of chronic phase CML the rest are.There are two cases of abnormal clones are four CML.2.3 FISH Cells without mistosis after culture of patients’bone marrow could be explored for bcr/abl fusion gene by FISH.Six cases of CML patientsin chronic phase were found Ph+ chromosome,which added the total Ph+ cases to 166 cases with a overall positive rate of Ph chromosome at 87.6%.3.Conclusion3.1 The typical karyotype in CML,t(9:22),were found in most cases with CML. Extra chromosome abnormalities were existed in a few patients in AP and BC.3.2 Cells without mistosis after culture of patients’ bone marrow could be complemented by FISH to explore bcr/abl fusion gene.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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