BH3 mimetics and TKI combined therapy for Chronic Myeloid Leukemia.
Gabriela BrumattiDeeksha KaloniFabíola Attié CastroGustavo P Amarante-MendesPublished in: The Biochemical journal (2023)
Chronic myeloid leukemia (CML) was considered for a long time one of the most hostile leukemia that was incurable for most of the patients, predominantly due to the extreme resistance to chemotherapy. Part of the resistance to cell death (apoptosis) is the result of increased levels of anti-apoptotic and decreased levels of pro-apoptotic member of the BCL-2 family induced by the BCR-ABL1 oncoprotein. BCR-ABL1 is a constitutively active tyrosine kinase responsible for initiating multiple and oncogenic signaling pathways. With the development of specific BCR-ABL1 tyrosine kinase inhibitors (TKIs) CML became a much more tractable disease. Nevertheless, TKIs do not cure CML patients and a substantial number of them develop intolerance or become resistant to the treatment. Therefore, novel anti-cancer strategies must be developed to treat CML patients independently or in combination with TKIs. Here, we will discuss the mechanisms of BCR-ABL1-dependent and -independent resistance to TKIs and the use of BH3-mimetics as a potential tool to fight CML.
Keyphrases
- chronic myeloid leukemia
- tyrosine kinase
- cell death
- end stage renal disease
- newly diagnosed
- ejection fraction
- prognostic factors
- peritoneal dialysis
- squamous cell carcinoma
- epidermal growth factor receptor
- oxidative stress
- acute lymphoblastic leukemia
- cell proliferation
- signaling pathway
- climate change
- risk assessment
- patient reported outcomes
- anti inflammatory
- bone marrow
- smoking cessation