Exploration of ETV6::ABL1-positive AML with concurrent NPM1 and FLT3-ITD mutations.

Autor: Li HD; Clinical Laboratory Medicine Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China., Chen SS; Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China., Ding J; Clinical Laboratory Medicine Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China., Zhang CL; Clinical Laboratory Medicine Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China., Qiu HY; Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China., Xia XX; Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China., Yang J; Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. yangjuan74@sina.com., Wang XR; Clinical Laboratory Medicine Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China. Xiaorui.wang@shgh.cn.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Oct; Vol. 103 (10), pp. 4295-4304. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1007/s00277-024-05917-3
Abstrakt: ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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