Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring
A minority of chronic myeloid leukemia patients (CML) express a variety of atypical BCR-ABL1 fusion variants and, of these, the e6a2 BCR-ABL1 fusion is generally associated with an aggressive disease course. Progression of CML to blast crisis is associated with acquisition of additional somatic muta...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Case Reports in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2017/9071702 |
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| author | Mireille Crampe Karl Haslam Emma Groarke Eileen Kelleher Derville O’Shea Eibhlin Conneally Stephen E. Langabeer |
| author_facet | Mireille Crampe Karl Haslam Emma Groarke Eileen Kelleher Derville O’Shea Eibhlin Conneally Stephen E. Langabeer |
| author_sort | Mireille Crampe |
| collection | DOAJ |
| description | A minority of chronic myeloid leukemia patients (CML) express a variety of atypical BCR-ABL1 fusion variants and, of these, the e6a2 BCR-ABL1 fusion is generally associated with an aggressive disease course. Progression of CML to blast crisis is associated with acquisition of additional somatic mutations yet these events have not been elucidated in patients with the e6a2 BCR-ABL1 genotype. Moreover, molecular monitoring is only sporadically performed in CML patients with atypical BCR-ABL1 fusion transcripts due to lack of consensus approaches or standardization. A case of CML is described in which comprehensive molecular analysis, including targeted next-generation sequencing, revealed a single ASXL1 mutation cooperating with an e6a2 BCR-ABL1 fusion transcript at blast crisis. A quantitative molecular monitoring approach was devised and adopted that reflected the disease response from initial treatment through allogeneic stem cell transplantation which resulted in undetectable e6a2 BCR-ABL1 transcripts. This case emphasizes the requirement for molecular monitoring in CML patients with atypical BCR-ABL1 fusion transcripts and emphasizes that comprehensive sequencing has the potential to identify targets for novel therapies in CML patients with advanced disease. |
| format | Article |
| id | doaj-art-63d3fbb0e30d40d489811df650453fd7 |
| institution | Kabale University |
| issn | 2090-6560 2090-6579 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Hematology |
| spelling | doaj-art-63d3fbb0e30d40d489811df650453fd72025-08-20T03:34:29ZengWileyCase Reports in Hematology2090-65602090-65792017-01-01201710.1155/2017/90717029071702Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular MonitoringMireille Crampe0Karl Haslam1Emma Groarke2Eileen Kelleher3Derville O’Shea4Eibhlin Conneally5Stephen E. Langabeer6Cancer Molecular Diagnostics, St. James’s Hospital, Dublin 8, IrelandCancer Molecular Diagnostics, St. James’s Hospital, Dublin 8, IrelandDepartment of Haematology, St. James’s Hospital, Dublin 8, IrelandDepartment of Haematology, Bon Secours Hospital, Cork, IrelandDepartment of Haematology, Cork University Hospital, Cork, IrelandDepartment of Haematology, St. James’s Hospital, Dublin 8, IrelandCancer Molecular Diagnostics, St. James’s Hospital, Dublin 8, IrelandA minority of chronic myeloid leukemia patients (CML) express a variety of atypical BCR-ABL1 fusion variants and, of these, the e6a2 BCR-ABL1 fusion is generally associated with an aggressive disease course. Progression of CML to blast crisis is associated with acquisition of additional somatic mutations yet these events have not been elucidated in patients with the e6a2 BCR-ABL1 genotype. Moreover, molecular monitoring is only sporadically performed in CML patients with atypical BCR-ABL1 fusion transcripts due to lack of consensus approaches or standardization. A case of CML is described in which comprehensive molecular analysis, including targeted next-generation sequencing, revealed a single ASXL1 mutation cooperating with an e6a2 BCR-ABL1 fusion transcript at blast crisis. A quantitative molecular monitoring approach was devised and adopted that reflected the disease response from initial treatment through allogeneic stem cell transplantation which resulted in undetectable e6a2 BCR-ABL1 transcripts. This case emphasizes the requirement for molecular monitoring in CML patients with atypical BCR-ABL1 fusion transcripts and emphasizes that comprehensive sequencing has the potential to identify targets for novel therapies in CML patients with advanced disease.http://dx.doi.org/10.1155/2017/9071702 |
| spellingShingle | Mireille Crampe Karl Haslam Emma Groarke Eileen Kelleher Derville O’Shea Eibhlin Conneally Stephen E. Langabeer Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring Case Reports in Hematology |
| title | Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring |
| title_full | Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring |
| title_fullStr | Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring |
| title_full_unstemmed | Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring |
| title_short | Chronic Myeloid Leukemia with an e6a2 BCR-ABL1 Fusion Transcript: Cooperating Mutations at Blast Crisis and Molecular Monitoring |
| title_sort | chronic myeloid leukemia with an e6a2 bcr abl1 fusion transcript cooperating mutations at blast crisis and molecular monitoring |
| url | http://dx.doi.org/10.1155/2017/9071702 |
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