Secondary fusion proteins as a mechanism of BCR::ABL1 kinase-independent resistance in chronic myeloid leukaemia.

Autor: Barnes EJ; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Eide CA; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Kaempf A; Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Bottomly D; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Romine KA; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Wilmot B; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Saunders D; Flow Cytometry Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., McWeeney SK; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Tognon CE; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Druker BJ; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2023 Feb; Vol. 200 (3), pp. 323-328. Date of Electronic Publication: 2022 Oct 20.
DOI: 10.1111/bjh.18515
Abstrakt: Drug resistance in chronic myeloid leukaemia (CML) may occur via mutations in the causative BCR::ABL1 fusion or BCR::ABL1-independent mechanisms. We analysed 48 patients with BCR::ABL1-independent resistance for the presence of secondary fusion genes by RNA sequencing. We identified 10 of the most frequently detected secondary fusions in 21 patients. Validation studies, cell line models, gene expression analysis and drug screening revealed differences with respect to proliferation rate, differentiation and drug sensitivity. Notably, expression of RUNX1::MECOM led to resistance to ABL1 tyrosine kinase inhibitors in vitro. These results suggest secondary fusions contribute to BCR::ABL1-independent resistance and may be amenable to combined therapies.
(© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: