BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia
- Author(s)
- Amarante-Mendes, GP; Rana, A; Datoguia, TS; Hamerschlak, N; Brumatti, G;
- Details
- Publication Year 2022-01-17,Volume 14,Issue #1,Page 215
- Journal Title
- Pharmaceutics
- Abstract
- The constitutively active BCR-ABL1 tyrosine kinase, found in t(9;22)(q34;q11) chromosomal translocation-derived leukemia, initiates an extremely complex signaling transduction cascade that induces a strong state of resistance to chemotherapy. Targeted therapies based on tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, have revolutionized the treatment of BCR-ABL1-driven leukemia, particularly chronic myeloid leukemia (CML). However, TKIs do not cure CML patients, as some develop TKI resistance and the majority relapse upon withdrawal from treatment. Importantly, although BCR-ABL1 tyrosine kinase is necessary to initiate and establish the malignant phenotype of Ph-related leukemia, in the later advanced phase of the disease, BCR-ABL1-independent mechanisms are also in place. Here, we present an overview of the signaling pathways initiated by BCR-ABL1 and discuss the major challenges regarding immunologic/pharmacologic combined therapies.
- Keywords
- Bcr-abl1; chronic myeloid leukemia; tyrosine kinase inhibitors
- Research Division(s)
- Inflammation
- PubMed ID
- 35057108
- Publisher's Version
- https://doi.org/10.3390/pharmaceutics14010215
- Open Access at Publisher's Site
https://doi.org/10.3390/pharmaceutics14010215- Terms of Use/Rights Notice
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Creation Date: 2022-02-18 11:36:28
Last Modified: 2022-02-18 12:58:47