Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia

Dorian Forte, Roberto Maria Pellegrino, Paolo Falvo, Paulina Garcia-Gonzalez, Husam B. R. Alabed, Filippo Maltoni, Davide Lombardi, Samantha Bruno, Martina Barone, Federico Pasini, Francesco Fabbri, Ivan Vannini, Benedetta Donati, Gianluca Cristiano, Chiara Sartor, Simona Ronzoni, Alessia Ciarrocchi, Sandra Buratta, Lorena Urbanelli, Carla Emiliani, Simona Soverini, Lucia Catani, Francesco Bertolini, Rafael José Argüello, Michele Cavo and Antonio Curti ()
Additional contact information
Dorian Forte: University of Bologna
Roberto Maria Pellegrino: University of Perugia
Paolo Falvo: European Institute of Oncology IRCCS
Paulina Garcia-Gonzalez: Centre d’Immunologie de Marseille-Luminy
Husam B. R. Alabed: University of Perugia
Filippo Maltoni: University of Bologna
Davide Lombardi: European Institute of Oncology IRCCS
Samantha Bruno: University of Bologna
Martina Barone: Istituto di Ematologia “Seràgnoli”
Federico Pasini: University of Bologna
Francesco Fabbri: IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”
Ivan Vannini: IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”
Benedetta Donati: Azienda USL-IRCCS di Reggio Emilia
Gianluca Cristiano: University of Bologna
Chiara Sartor: University of Bologna
Simona Ronzoni: European Institute of Oncology IRCCS
Alessia Ciarrocchi: Azienda USL-IRCCS di Reggio Emilia
Sandra Buratta: University of Perugia
Lorena Urbanelli: University of Perugia
Carla Emiliani: University of Perugia
Simona Soverini: University of Bologna
Lucia Catani: University of Bologna
Francesco Bertolini: European Institute of Oncology IRCCS
Rafael José Argüello: Centre d’Immunologie de Marseille-Luminy
Michele Cavo: University of Bologna
Antonio Curti: Istituto di Ematologia “Seràgnoli”

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML.

Date: 2024
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DOI: 10.1038/s41467-024-55231-9

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