A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case
Abstract Background Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is it...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13039-017-0322-8 |
| _version_ | 1811278580985888768 |
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| author | Fen Zhou Runming Jin Yu Hu Heng Mei |
| author_facet | Fen Zhou Runming Jin Yu Hu Heng Mei |
| author_sort | Fen Zhou |
| collection | DOAJ |
| description | Abstract Background Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones. The oncoprotein tyrosine kinase BCR-ABL1 is a constitutively active kinase involved in the activation of a number of signaling pathways, and it has been the therapeutic target for tyrosine kinase inhibitors (TKIs) such as imatinib. Reports have presented opposing viewpoints about the effect of the disrupted Src homology 3 (SH3) domain on TKI efficacy. Findings We here report that using NGS we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, leading to partial deletion of its SH3 domain. In the present case, the patient received targeted therapy with the TKI imatinib at 400 mg/day and no adverse reaction was reported. The patient eventually entered remission with decreased proliferation of karyocytes and granulocytes. We also identified mutations in genes, including TP53, FLT3, ASXL1, SETBP1, CEBPA and CBL, that seemed to have an influence on the outcome of TKI therapy targeting the BCR-ABL1 protein. Conclusions Together with previously reported results, it is clear that the genetic heterogeneity of CML patients significantly affects the presentation of the disease and its progression and therefore should inform the design of the therapeutic strategy. |
| first_indexed | 2024-04-13T00:38:24Z |
| format | Article |
| id | doaj.art-f597b8b61270493cb442932bc46b5d1e |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-04-13T00:38:24Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cytogenetics |
| spelling | doaj.art-f597b8b61270493cb442932bc46b5d1e2022-12-22T03:10:17ZengBMCMolecular Cytogenetics1755-81662017-05-011011510.1186/s13039-017-0322-8A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia caseFen Zhou0Runming Jin1Yu Hu2Heng Mei3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & TechnologyInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & TechnologyInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & TechnologyInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & TechnologyAbstract Background Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones. The oncoprotein tyrosine kinase BCR-ABL1 is a constitutively active kinase involved in the activation of a number of signaling pathways, and it has been the therapeutic target for tyrosine kinase inhibitors (TKIs) such as imatinib. Reports have presented opposing viewpoints about the effect of the disrupted Src homology 3 (SH3) domain on TKI efficacy. Findings We here report that using NGS we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, leading to partial deletion of its SH3 domain. In the present case, the patient received targeted therapy with the TKI imatinib at 400 mg/day and no adverse reaction was reported. The patient eventually entered remission with decreased proliferation of karyocytes and granulocytes. We also identified mutations in genes, including TP53, FLT3, ASXL1, SETBP1, CEBPA and CBL, that seemed to have an influence on the outcome of TKI therapy targeting the BCR-ABL1 protein. Conclusions Together with previously reported results, it is clear that the genetic heterogeneity of CML patients significantly affects the presentation of the disease and its progression and therefore should inform the design of the therapeutic strategy.http://link.springer.com/article/10.1186/s13039-017-0322-8CMLBCR-ABL1NGSSH3 domainGenetic heterogeneity |
| spellingShingle | Fen Zhou Runming Jin Yu Hu Heng Mei A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case Molecular Cytogenetics CML BCR-ABL1 NGS SH3 domain Genetic heterogeneity |
| title | A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| title_full | A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| title_fullStr | A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| title_full_unstemmed | A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| title_short | A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| title_sort | novel bcr abl1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case |
| topic | CML BCR-ABL1 NGS SH3 domain Genetic heterogeneity |
| url | http://link.springer.com/article/10.1186/s13039-017-0322-8 |
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