Dormant leukaemic stem cells could be eliminated by targeting a specific iron metabolism process, a new study has suggested.
The Swiss and French researchers say their findings could pave the way for new therapeutic strategies for tackling the dormant stem cells that are responsible for relapse of acute myeloid leukaemia (AML).
In the study, reported in Science Translational Medicine, the researchers identified differences in the activity of genes in dormant, or ‘quiescent’, leukaemia stem cells, compared to actively proliferating leukaemia cells.
“Using advanced bioinformatics techniques and in collaboration with the team of Dr Petros Tsantoulis from the Department of Oncology and Precision Oncology at the University Hospital of Geneva, we first established that these quiescent cells contain a unique genetic signature consisting of 35 genes,” said Researcher Dr Jérôme Tamburini, of the Swiss Cancer Centre Léman.
“When we used this signature in large clinical databases of patients with acute myeloid leukaemia, we were able to show that this signature was strongly linked to the prognosis of the disease.”
Investigating the metabolic characteristics of dormant leukaemia stem cells, the researchers found that they have a particular ability to use the iron storage molecule, ferritin, in the process of recycling cellular components.
The laboratory studies suggest that the protein NCOA4 is involved in this process. When NCOA4 was blocked, either genetically or with a small drug-like compound, the leukaemic stem cells died while healthy blood stem cells remain intact.
The research involved the University of Geneva and the University Hospital of Geneva in Switzerland, working with researchers at Inserm in France and Professor Jun Xu, of Sun Yat-Sen University, China.
The compound used to block NCOA4 is now in the early stages of development for future clinical trials.
Source:
Larrue C, Mouche S, Angelino P, Sajot M, Birsen R, Kosmider O, Mckee T, Vergez F, Recher C, Mas VM, Gu Q, Xu J, Tsantoulis P, Sarry JE, Tamburini J. (2024) “Targeting ferritinophagy impairs quiescent cancer stem cells in acute myeloid leukemia in vitro and in vivo models.” Science Translational Medicine, 24 July 2024, doi: 10.1126/scitranslmed.adk1731.
Link: https://www.science.org/doi/10.1126/scitranslmed.adk1731
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