Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia
Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34<sup>+</sup>(CD38<sup>low/-</sup>) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34<sup>+</sup> AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Paulina A García-González
- Davide Lombardi (ORCID: https://orcid.org/0000-0003-3352-7231)
- Alessia Ciarrocchi (ORCID: https://orcid.org/0000-0002-5541-2075)
- Simona Soverini (ORCID: https://orcid.org/0000-0002-4508-0353)
- Dorian Forte (ORCID: https://orcid.org/0000-0002-8443-605X)
- Carla Emiliani (ORCID: https://orcid.org/0000-0002-6368-1515)
- Rafael J. Argüello (ORCID: https://orcid.org/0000-0001-9785-3883)
- Chiara Sartor (ORCID: https://orcid.org/0000-0002-2356-5691)
- Benedetta Donati (ORCID: https://orcid.org/0000-0002-9163-8194)
- Filippo Maltoni
- Martina Barone (ORCID: https://orcid.org/0000-0003-3356-9861)
- Simona Ronzoni (ORCID: https://orcid.org/0000-0002-3976-3406)
- Felice Pasini
- Francesco� Fabbri (ORCID: https://orcid.org/0000-0002-7885-3025)
- Ivan Vannini (ORCID: https://orcid.org/0000-0002-9279-1801)
- Paolo Falvo (ORCID: https://orcid.org/0000-0001-5743-5046)
- Husam B. R. Alabed (ORCID: https://orcid.org/0000-0002-9229-088X)
- Sandra Buratta (ORCID: https://orcid.org/0000-0002-9875-0138)
- Francesco Bertolini (ORCID: https://orcid.org/0000-0001-5660-3255)
- Michèle Cavo (ORCID: https://orcid.org/0000-0003-4514-3227)
- Antonio Curti (ORCID: https://orcid.org/0000-0002-7752-6049)
- Gianluca Cristiano (ORCID: https://orcid.org/0000-0002-8207-6038)
- Lorena Urbanelli (ORCID: https://orcid.org/0000-0003-0621-8476)
- Lucia Catani (ORCID: https://orcid.org/0000-0002-4650-201X)
- Samantha Bruno (ORCID: https://orcid.org/0000-0001-6375-0595)
- Roberto Maria Pellegrino (ORCID: https://orcid.org/0000-0001-5594-383X)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Perugia (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Istituto di Ematologia di Bologna (IT)
- Azienda USL di Bologna (IT)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- European Institute of Oncology (IT)
- University of Bologna (IT)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55231-9
- Citations
- 12
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 5.45
Funders
- Ministero della Salute
- Università degli Studi di Padova
- Fondazione Umberto Veronesi
- Associazione Italiana per la Ricerca sul Cancro
- Associazione Italiana Contro le Leucemie-Linfomi e Mieloma
- Agenzia Italiana del Farmaco, Ministero della Salute