The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease
碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 93 === Chromosome abnormalities were found in 80% to 90% of childhood acute lymphoblastic leukemia (ALL) cases. These leukemia-specific chromosome aberrations not only have prognostic value but also provide important clues for further investigation of leukogenesis , le...
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ndltd-TW-093KMC055340052015-10-13T13:08:18Z http://ndltd.ncl.edu.tw/handle/50080739003767682043 The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease TEL-AML1及BCR-ABL(p190)融合基因變異在南台灣小兒急性淋巴性白血病之盛行率以及應用在細微殘存疾病之偵測價值評估研究 Pei-Chin Lin 林佩瑾 碩士 高雄醫學大學 醫學研究所碩士班 93 Chromosome abnormalities were found in 80% to 90% of childhood acute lymphoblastic leukemia (ALL) cases. These leukemia-specific chromosome aberrations not only have prognostic value but also provide important clues for further investigation of leukogenesis , leukemic cell transformation and proliferation. Since the first fusion gene , BCR-ABL in t(9;22) , was discovered , many other chromosome aberrations with fusion genes have been identified. For instance , t(12;21) with TEL-AML1 fusion gene have been noted as the most frequent rearrangement in child hood ALL, whereas t(4;11) with MLL-AF4 fusion gene has been identified particularly in infant ALL. Advancement in molecular biology leads to accurate detection of these leukemia-specific chromosome aberrations with sensitive techniques, such as fluorescence in situ hybridization (FISH) , Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Leukemia-specific fusion genes have been used as molecular markers for minimal residual disease (MRD) monitoring. The remaining leukemic cells below the threshold of cytomorphological techniques (sensitivity around 1%~5%) was referred to as MRD. Several studies showed that existence of MRD during the maintenance phase is a independent poor prognostic factor. Monitoring MRD at consecutive time points can give clinical relevant insight into the effectiveness of treatment. In the present study, we apply RT-PCR technique in the detection of two leukemia-specific chromosome fusion genes, TEL-AML1 fusion gene and BCR-ABL p190 fusion gene. We also monitor the expression level of these fusion genes at sequential time points of the treatment course. Twenty-nine patients were enrolled in the study including 20 newly-diagnosed ALL, 5 relapsed ALL, 2 newly-diagnosed AML , 1 relapsed AML and one JMML. Of total 25 ALL cases, TEL-AML1 fusion gene was detected in 8 patients (6 newly-diagnosed and 2 relapsed cases) and BCR-ABL p190 was detected in only 2 newly-diagnosed cases. The incidence of TEL-AML1 fusion gene and BCR-ABL p190 fusion gene in our cases were 32 % and 10 % respectively. The clinical features of our eight TML-AML1 positive ALL cases were similar to the other studies except two of them were younger than 12 months old. Also, no t(12;21) was detected by the conventional cytogenetic study in our cases as it was identified as a cryptic chromosome translocation. All cases but one (TML-AML1 negative and BCR-ABL p190 negative) achieved cytomorphological remission after induction therapy and one patient among the 8 TML-AML1 positive cases relapsed during the consolidation phase. The other 18 newly-diagnosed ALL patients remained in remission status with follow-up period ranged from 1 month to 24 months. Blotting analysis was used for minimal residual disease detection by TEL-AML1 fusion transcript in the eight TML-AML1 positive ALL patients. Among six patients whose bone marrow or peripheral blood samples were obtained after treatment , reduction of TEL-AML1 expression levels were found in four. For further investigation of the accuracy and clinical implication of our methods , more experience and a large study group will be needed. Tai-Tsung Chang 張泰琮 2005 學位論文 ; thesis 60 zh-TW |
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碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 93 === Chromosome abnormalities were found in 80% to 90% of childhood acute lymphoblastic leukemia (ALL) cases. These leukemia-specific chromosome aberrations not only have prognostic value but also provide important clues for further investigation of leukogenesis , leukemic cell transformation and proliferation. Since the first fusion gene , BCR-ABL in t(9;22) , was discovered , many other chromosome aberrations with fusion genes have been identified. For instance , t(12;21) with TEL-AML1 fusion gene have been noted as the most frequent rearrangement in child hood ALL, whereas t(4;11) with MLL-AF4 fusion gene has been identified particularly in infant ALL. Advancement in molecular biology leads to accurate detection of these leukemia-specific chromosome aberrations with sensitive techniques, such as fluorescence in situ hybridization (FISH) , Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Leukemia-specific fusion genes have been used as molecular markers for minimal residual disease (MRD) monitoring. The remaining leukemic cells below the threshold of cytomorphological techniques (sensitivity around 1%~5%) was referred to as MRD. Several studies showed that existence of MRD during the maintenance phase is a independent poor prognostic factor. Monitoring MRD at consecutive time points can give clinical relevant insight into the effectiveness of treatment. In the present study, we apply RT-PCR technique in the detection of two leukemia-specific chromosome fusion genes, TEL-AML1 fusion gene and BCR-ABL p190 fusion gene. We also monitor the expression level of these fusion genes at sequential time points of the treatment course. Twenty-nine patients were enrolled in the study including 20 newly-diagnosed ALL, 5 relapsed ALL, 2 newly-diagnosed AML , 1 relapsed AML and one JMML. Of total 25 ALL cases, TEL-AML1 fusion gene was detected in 8 patients (6 newly-diagnosed and 2 relapsed cases) and BCR-ABL p190 was detected in only 2 newly-diagnosed cases. The incidence of TEL-AML1 fusion gene and BCR-ABL p190 fusion gene in our cases were 32 % and 10 % respectively. The clinical features of our eight TML-AML1 positive ALL cases were similar to the other studies except two of them were younger than 12 months old. Also, no t(12;21) was detected by the conventional cytogenetic study in our cases as it was identified as a cryptic chromosome translocation. All cases but one (TML-AML1 negative and BCR-ABL p190 negative) achieved cytomorphological remission after induction therapy and one patient among the 8 TML-AML1 positive cases relapsed during the consolidation phase. The other 18 newly-diagnosed ALL patients remained in remission status with follow-up period ranged from 1 month to 24 months.
Blotting analysis was used for minimal residual disease detection by TEL-AML1 fusion transcript in the eight TML-AML1 positive ALL patients. Among six patients whose bone marrow or peripheral blood samples were obtained after treatment , reduction of TEL-AML1 expression levels were found in four. For further investigation of the accuracy and clinical implication of our methods , more experience and a large study group will be needed.
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author2 |
Tai-Tsung Chang |
author_facet |
Tai-Tsung Chang Pei-Chin Lin 林佩瑾 |
author |
Pei-Chin Lin 林佩瑾 |
spellingShingle |
Pei-Chin Lin 林佩瑾 The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
author_sort |
Pei-Chin Lin |
title |
The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
title_short |
The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
title_full |
The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
title_fullStr |
The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
title_full_unstemmed |
The incidence of TEL-AML1 and BCR-ABL(p190) fusion transcripts in childhood acute lymphoblastic leukemia of Southern Taiwan and application of the fusion transcripts in the detection of minimal residual disease |
title_sort |
incidence of tel-aml1 and bcr-abl(p190) fusion transcripts in childhood acute lymphoblastic leukemia of southern taiwan and application of the fusion transcripts in the detection of minimal residual disease |
publishDate |
2005 |
url |
http://ndltd.ncl.edu.tw/handle/50080739003767682043 |
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