Researchers have made a significant breakthrough in the battle against Acute Myeloid Leukemia (AML), one of the most dangerous forms of cancer. By uncovering specific genetic and metabolic traits of leukaemic stem cells, such as a unique iron utilization process, they have found a way to potentially weaken or eliminate these cells while sparing healthy ones. These findings hold promise for the development of innovative treatment approaches.
AML is a prevalent type of blood and bone marrow cancer in adults, characterized by the rapid proliferation of immature cells that replace healthy blood cells, leading to severe health complications. Unfortunately, AML has a high mortality rate, especially among older individuals.
The challenge in treating AML lies in the existence of dormant leukaemic stem cells that are resistant to conventional therapies and can reawaken to reignite the disease post-treatment. Unraveling the mechanisms that govern these cells is crucial for devising effective treatment strategies.
By pinpointing the distinct genetic and metabolic features of leukaemic stem cells, researchers have shed new light on potential therapeutic avenues. These breakthroughs, documented in the journal Science Translational Medicine, offer a new target for therapy with promising clinical implications.
Triumph in Genetic Analysis
Advanced bioinformatics tools were instrumental in identifying a unique genetic signature comprising 35 genes specific to quiescent leukaemic cells. Analysis of large patient databases revealed a strong correlation between this genetic signature and disease prognosis, propelling our understanding of AML progression.
Disruption of Nutrient Utilization
Research has also unveiled a metabolic divergence between dormant and active leukaemic stem cells. These cells rely on a process called ”ferritinophagy”, a type of autophagy that targets ferritin, the principal iron-storage molecule. Inhibiting this process, controlled by the NCOA4 protein, resulted in the selective elimination of leukaemia cells, particularly dormant stem cells, while leaving healthy blood stem cells unscathed.
Advancing to Clinical Trials
Experiments on mouse models have corroborated the efficacy of inhibiting the NCOA4 protein in diminishing tumour growth and the viability of leukaemic stem cells. Targeting ferritinophagy through this pathway holds promise as a potential therapeutic strategy. The compound for NCOA4 inhibition is currently in its nascent stages of development for future clinical trials spearheaded by Jun Xu, a professor at Sun Yat-Sen University in China, and one of the study’s co-authors.
The research team at UNIGE is poised to delve deeper into the mechanisms of ferritinophagy and explore its interplay with mitophagy, another crucial regulator of leukaemic stem cells. This future research phase is generously funded by the Swiss Cancer League.
