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

• Main Authors: Pei-Chin Lin, 林佩瑾
• Other Authors: Tai-Tsung Chang
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/50080739003767682043

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.