Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion
Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00359/full |
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| author | Hai-Ping Dai Hai-Ping Dai Hai-Ping Dai Jia Yin Jia Yin Jia Yin Zheng Li Zheng Li Zheng Li Chun-Xiao Yang Tin Cao Ping Chen Yun-Hui Zong Ming-Qing Zhu Ming-Qing Zhu Ming-Qing Zhu Xia-Ming Zhu Xia-Ming Zhu Xia-Ming Zhu Sheng Xiao De-Pei Wu De-Pei Wu De-Pei Wu Xiao-Wen Tang Xiao-Wen Tang Xiao-Wen Tang |
| author_facet | Hai-Ping Dai Hai-Ping Dai Hai-Ping Dai Jia Yin Jia Yin Jia Yin Zheng Li Zheng Li Zheng Li Chun-Xiao Yang Tin Cao Ping Chen Yun-Hui Zong Ming-Qing Zhu Ming-Qing Zhu Ming-Qing Zhu Xia-Ming Zhu Xia-Ming Zhu Xia-Ming Zhu Sheng Xiao De-Pei Wu De-Pei Wu De-Pei Wu Xiao-Wen Tang Xiao-Wen Tang Xiao-Wen Tang |
| author_sort | Hai-Ping Dai |
| collection | DOAJ |
| description | Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors.Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT.Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing.Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion. |
| first_indexed | 2024-12-10T07:51:32Z |
| format | Article |
| id | doaj.art-1989c545c0374c69821ed41db97581cd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T07:51:32Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1989c545c0374c69821ed41db97581cd2022-12-22T01:57:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-03-011010.3389/fonc.2020.00359521142Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN FusionHai-Ping Dai0Hai-Ping Dai1Hai-Ping Dai2Jia Yin3Jia Yin4Jia Yin5Zheng Li6Zheng Li7Zheng Li8Chun-Xiao Yang9Tin Cao10Ping Chen11Yun-Hui Zong12Ming-Qing Zhu13Ming-Qing Zhu14Ming-Qing Zhu15Xia-Ming Zhu16Xia-Ming Zhu17Xia-Ming Zhu18Sheng Xiao19De-Pei Wu20De-Pei Wu21De-Pei Wu22Xiao-Wen Tang23Xiao-Wen Tang24Xiao-Wen Tang25National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaSano Suzhou Precision Medicine Co., Ltd., Suzhou, ChinaSano Suzhou Precision Medicine Co., Ltd., Suzhou, ChinaSano Suzhou Precision Medicine Co., Ltd., Suzhou, ChinaSano Suzhou Precision Medicine Co., Ltd., Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaDepartment of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United StatesNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaBackground: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors.Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT.Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing.Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.https://www.frontiersin.org/article/10.3389/fonc.2020.00359/fullNCOR1-LYNfusion genedasatinibALLpediatric |
| spellingShingle | Hai-Ping Dai Hai-Ping Dai Hai-Ping Dai Jia Yin Jia Yin Jia Yin Zheng Li Zheng Li Zheng Li Chun-Xiao Yang Tin Cao Ping Chen Yun-Hui Zong Ming-Qing Zhu Ming-Qing Zhu Ming-Qing Zhu Xia-Ming Zhu Xia-Ming Zhu Xia-Ming Zhu Sheng Xiao De-Pei Wu De-Pei Wu De-Pei Wu Xiao-Wen Tang Xiao-Wen Tang Xiao-Wen Tang Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion Frontiers in Oncology NCOR1-LYN fusion gene dasatinib ALL pediatric |
| title | Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion |
| title_full | Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion |
| title_fullStr | Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion |
| title_full_unstemmed | Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion |
| title_short | Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion |
| title_sort | rapid molecular response to dasatinib in a pediatric relapsed acute lymphoblastic leukemia with ncor1 lyn fusion |
| topic | NCOR1-LYN fusion gene dasatinib ALL pediatric |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00359/full |
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