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

Author

Listed:
  • Dorian Forte

    (University of Bologna)

  • Roberto Maria Pellegrino

    (University of Perugia)

  • Paolo Falvo

    (European Institute of Oncology IRCCS
    European Institute of Oncology IRCCS and Politecnico di Milano)

  • Paulina Garcia-Gonzalez

    (Centre d’Immunologie de Marseille-Luminy)

  • Husam B. R. Alabed

    (University of Perugia)

  • Filippo Maltoni

    (University of Bologna
    Istituto di Ematologia “Seràgnoli”)

  • Davide Lombardi

    (European Institute of Oncology IRCCS
    European Institute of Oncology IRCCS and Politecnico di Milano)

  • 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
    Istituto di Ematologia “Seràgnoli”)

  • 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
    University of Perugia)

  • Simona Soverini

    (University of Bologna)

  • Lucia Catani

    (University of Bologna
    Istituto di Ematologia “Seràgnoli”)

  • Francesco Bertolini

    (European Institute of Oncology IRCCS
    European Institute of Oncology IRCCS and Politecnico di Milano)

  • Rafael José Argüello

    (Centre d’Immunologie de Marseille-Luminy)

  • Michele Cavo

    (University of Bologna
    Istituto di Ematologia “Seràgnoli”)

  • Antonio Curti

    (Istituto di Ematologia “Seràgnoli”)

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.

Suggested Citation

  • 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, 2024. "Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55231-9
    DOI: 10.1038/s41467-024-55231-9
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