An worldwide group of researchers has identified how acute myeloid leukemia (AML) cells manage to continue growing. These AML cells hinder the production of proteins that would normally limit their growth by trapping the mRNAs that would create those proteins inside structures called P-bodies. This discovery sheds new light on how AML survives and points the way to potential new cancer treatments.
An worldwide group of researchers has identified how acute myeloid leukemia (AML) cells manage to continue growing.
A team from Baylor College of Medicine, University of Veterinary Medicine in Austria, and Josep Carreras Leukemia Research Institute in Spain found that AML cells hinder the production of growth-suppressing proteins by trapping the mRNAs needed to create these proteins in P-bodies. Their findings, detailed in Nature Cell Biology, provide fresh insights into how AML cells survive and suggest new opportunities for anti-cancer therapies.
“Even with significant progress in cancer research, the outlook for many AML patients is still bleak,” noted Dr. Bruno Di Stefano, assistant professor of molecular and cellular biology and part of Baylor’s Stem Cell and Regenerative Medicine (STaR) Center. “We aimed to uncover and thoroughly understand new weaknesses in leukemia cells that could be targeted for therapy in AML.”
Past research has indicated that leukemia cells manipulate the mRNA-to-protein translation process in ways that promote their growth, but the precise mechanisms remain unclear.
“Our initial clue about how leukemia cells might disrupt normal translation control came from observing that they contained more P-bodies than healthy cells,” explained Di Stefano, a member of the Dan L Duncan Comprehensive Cancer Center. “Interestingly, P-bodies proved vital for the survival of leukemia cells but were not necessary for normal blood cells, indicating a possible specific requirement in AML.”
P-bodies are biomolecular structures that gather proteins and RNA within cells. They act as storage hubs, keeping certain mRNAs away from the cellular machinery that would convert them into proteins. “We consider P-bodies to be storage compartments for RNAs,” Di Stefano remarked.
The researchers studied the mRNAs found in the P-bodies of AML cells. “We found that these leukemia cells stash away mRNAs that code for tumor-suppressing proteins in their P-bodies,” said Di Stefano. “Crucially, these mRNAs were not broken down, and when we broke apart P-bodies, we discovered that the mRNAs could be converted into proteins that can inhibit AML.”
“In fact, eliminating P-bodies by removing DDX6, a protein crucial for their formation, caused cancer cells to die in various human AML models, across different subtypes and mutations,” stated Dr. José L. Sardina, principal investigator at Josep Carreras Leukemia Research Institute. “AML is a diverse disease, and finding a common molecular weakness is incredibly exciting. Importantly, the loss of P-bodies had minimal impact on normal blood cell production, emphasizing the potential of targeting P-body formation in AML.”
“The revelation that AML cells rely on P-bodies and the mechanisms involved has several significant implications,” added Dr. Florian Grebien, professor of medical biochemistry at the University of Veterinary Medicine, Vienna. “Firstly, it offers new insights into the less understood process of mRNA translation regulation in cancer. Secondly, since DDX6 is a druggable target, our findings pave the way for the creation of new anticancer treatments that focus on this mechanism.”
