Genomic amplification of BCR-ABL1 fusion gene and its impact on the disease progression mechanism in patients with chronic myelogenous leukemia
| Autor: | Preethi Gopinath, Thampirajan Vimaladevi Akhila Raj, Kunnathur Murugesan Sakthivel, Jagathnath Krishna Kumarapillai Mohanan Nair, Ramachandran Krishna Chandran, Hariharan Sreedharan, Geetha Priya, Narayanan Geetha, Chandran Geetha Aswathy |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent medicine.medical_treatment Fusion Proteins bcr-abl BCR/ABL1 Fusion Gene Biology Targeted therapy Fusion gene 03 medical and health sciences 0302 clinical medicine Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Genetics medicine Humans Philadelphia Chromosome In Situ Hybridization Fluorescence Aged Aged 80 and over ABL medicine.diagnostic_test Gene Amplification breakpoint cluster region General Medicine Middle Aged medicine.disease Chromosome Banding 030104 developmental biology Imatinib mesylate 030220 oncology & carcinogenesis Cancer research Female Chronic myelogenous leukemia Fluorescence in situ hybridization |
| Zdroj: | Gene. 686:85-91 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2018.11.005 |
| Popis: | Identification of BCR-ABL1 fusion gene amplification status is critically important in the effective management of chronic myelogenous leukemia (CML) patients. Earlier reports suggested that overexpression of BCR-ABL1 either through amplification of BCR-ABL1 fusion gene or by the up regulation of BCR-ABL1 transcript level might be an early phenomenon in the establishment of IM resistance and disease evolution in CML. In the current study, we performed dual color dual fusion locus specific BCR/ABL1 FISH analysis along with karyotype analysis using GTG banding (G-banding using trypsin and Giemsa) technique in 489 patients with different clinical stages of CML at diagnosis or during the course of the disease to unravel the spectrum of BCR-ABL1 fusion gene amplification status. Among the study group analyzed, it was found that prevalence of occurrence of BCR-ABL1 fusion gene amplification was significantly higher in advanced stages of disease and in IM resistant CML-CP patients when compared to initial stage of disease, de novo CML-CP. Cytogenetic and metaphase FISH characterization on our study samples revealed that BCR-ABL1 fusion gene amplification was occurred through the formation of extra copies Ph chromosomes and isoderived Ph chromosomes. Current study suggests that unrestrained activity of BCR-ABL1 played a vital role in resistance to targeted therapy and disease evolution in CML. In our study population, patients in progressive stage CML and in IM resistant CP with multiple copies of BCR-ABL1 fusion gene displayed a poor response to targeted treatment with IM. Hence, the early identification of BCR-ABL1 fusion gene amplification using FISH technique will lead to improved interventions and outcome in future CML patients. |
| Databáze: | OpenAIRE |
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