Scientists from the National University of Singapore (NUS) have discovered that the evasion of apoptosis is a key driver of drug resistance in patients with relapsed acute myeloid leukaemia (AML), a type of aggressive blood cancer.
Mar 19 2024National University of Singapore Scientists from the National University of Singapore have discovered that the evasion of apoptosis is a key driver of drug resistance in patients with relapsed acute myeloid leukaemia , a type of aggressive blood cancer. The results are expected to contribute towards the identification of effective drugs for treating relapsed patients.
The research team led by Assistant Professor Shruti Bhatt from the NUS Department of Pharmacy and Pharmaceutical Sciences has identified the potential mechanism behind multi-drug resistance in relapsed AML patients. They also highlighted the effectiveness of a technique, called dynamic BH3 profiling , in identifying anti-cancer drugs capable of targeting relapsed leukaemia cells.
The research team established in vivo models of acquired resistance to a spectrum of clinically relevant anti-cancer drugs using patient-derived xenograft models. Subsequently, they conducted a comprehensive analysis encompassing genomics, transcriptomics, and functional studies on drug-resistant AML models. Intriguingly, their investigations revealed a common point for resistance induced by various drugs: the mitochondria.
To address this challenge, the researchers used dynamic BH3 profiling , a technique involving short-term treatment of leukaemia cells derived from therapy-resistant preclinical models with a panel of clinically relevant drugs. Mitochondrial apoptotic signalling is then measured to determine drugs capable of overcoming resistance.