Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia
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 glutathi...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55231-9 |
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| author | 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 Antonio Curti |
| author_facet | 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 Antonio Curti |
| author_sort | Dorian Forte |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d9ce876d888c4a418e451ddc1c94c6d2 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d9ce876d888c4a418e451ddc1c94c6d22025-01-05T12:35:31ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-55231-9Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemiaDorian Forte0Roberto Maria Pellegrino1Paolo Falvo2Paulina Garcia-Gonzalez3Husam B. R. Alabed4Filippo Maltoni5Davide Lombardi6Samantha Bruno7Martina Barone8Federico Pasini9Francesco Fabbri10Ivan Vannini11Benedetta Donati12Gianluca Cristiano13Chiara Sartor14Simona Ronzoni15Alessia Ciarrocchi16Sandra Buratta17Lorena Urbanelli18Carla Emiliani19Simona Soverini20Lucia Catani21Francesco Bertolini22Rafael José Argüello23Michele Cavo24Antonio Curti25Department of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaDepartment of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences Section, University of PerugiaLaboratory of Hematology-Oncology, European Institute of Oncology IRCCSAix Marseille Univ, CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-LuminyDepartment of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences Section, University of PerugiaDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaLaboratory of Hematology-Oncology, European Institute of Oncology IRCCSDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”Department of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Laboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaDepartment of Experimental Oncology, European Institute of Oncology IRCCSLaboratory of Translational Research, Azienda USL-IRCCS di Reggio EmiliaDepartment of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences Section, University of PerugiaDepartment of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences Section, University of PerugiaDepartment of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences Section, University of PerugiaDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaLaboratory of Hematology-Oncology, European Institute of Oncology IRCCSAix Marseille Univ, CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-LuminyDepartment of Medical and Surgical Sciences, Institute of Hematology “L. and A. Seràgnoli”, University of BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, 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.https://doi.org/10.1038/s41467-024-55231-9 |
| spellingShingle | 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 Antonio Curti Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia Nature Communications |
| title | Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| title_full | Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| title_fullStr | Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| title_full_unstemmed | Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| title_short | Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| title_sort | parallel single cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia |
| url | https://doi.org/10.1038/s41467-024-55231-9 |
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