https://scholars.lib.ntu.edu.tw/handle/123456789/597094
標題: | A Novel Tandem Duplication Assay to Detect Minimal Residual Disease in FLT3/ITD AML | 作者: | Lin M.-T. LI-HUI TSENG Dudley J.C. Riel S. Tsai H. Zheng G. Pratz K.W. Levis M.J. Gocke C.D. |
公開日期: | 2015 | 出版社: | Springer International Publishing | 卷: | 19 | 期: | 6 | 起(迄)頁: | 409-417 | 來源出版物: | Molecular Diagnosis and Therapy | 摘要: | Background: Internal tandem duplication (ITD) of the fms-related tyrosine kinase?3 (FLT3) gene is associated with a poor prognosis in acute myeloid leukemia (AML) patients with a normal karyotype. The current standard polymerase chain reaction (PCR) assay for FLT3/ITD detection is not sufficiently sensitive to monitor minimal residual disease (MRD). Clone-specific assays may have sufficient sensitivity but are not practical to implement, since each clone-specific primer/probe requires clinical validation. Objective: To develop an assay for clinical molecular diagnostics laboratories to monitor MRD in FLT3/ITD AMLs. Methods: We designed a simple novel assay, tandem duplication PCR (TD-PCR), and tested its sensitivity, specificity, and clinical utility in FLT3/ITD AML patients. Results: TD-PCR was capable of detecting a single ITD molecule and was applicable to 75?% of ITD mutants tested. TD-PCR detected MRD in bone marrow prior to patient relapse. TD-PCR also identified low-level ITD mutants not only in FLT3/ITD AMLs but also in initial diagnostic specimens that were reportedly negative by the standard assay in patients who progressed with the same ITDs detected by the TD-PCR assay. Conclusion: Detection of MRD by TD-PCR may guide patient selection for early clinical intervention. In contrast to clone-specific approaches, the TD-PCR assay can be more easily validated for MRD detection in clinical laboratories because it uses standardized primers and a universal positive control. In addition, our findings on multi-clonality and low-level ITDs suggest that further studies are warranted to elucidate their clinical/biological significance. ? 2015, Springer International Publishing Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84947618072&doi=10.1007%2fs40291-015-0170-3&partnerID=40&md5=899f2d0e7cf4c44ba54122cc6431db9c https://scholars.lib.ntu.edu.tw/handle/123456789/597094 |
ISSN: | 1177-1062 | DOI: | 10.1007/s40291-015-0170-3 | SDG/關鍵字: | CD135 antigen; CD135 antigen; FLT3 protein, human; acute myeloblastic leukemia; Article; cancer diagnosis; diagnostic test accuracy study; gene duplication; gene mutation; human; human cell; internal tandem duplication polymerase chain reaction; leukemia relapse; leukemia remission; major clinical study; minimal residual disease; molecular diagnostics; polymerase chain reaction; priority journal; sensitivity and specificity; dna mutational analysis; gene duplication; genetics; Leukemia, Myeloid, Acute; minimal residual disease; molecular diagnosis; polymerase chain reaction; DNA Mutational Analysis; fms-Like Tyrosine Kinase 3; Gene Duplication; Humans; Leukemia, Myeloid, Acute; Molecular Diagnostic Techniques; Neoplasm, Residual; Polymerase Chain Reaction; Sensitivity and Specificity |
顯示於: | 基因體暨蛋白體醫學研究所 |
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