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Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia |
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| Authors: | Diego A. Pereira-Martins,Juan L. Coelho-Silva,Isabel Weinhäuser,Pedro L. Franca-Neto,Douglas R. Silveira,César Ortiz,Amanda Moreira-Aguiar,Marinus M. Lima,Luisa C. Koury,Raul A. de Melo,Ana B. Glória,Evandro M. Fagundes,Bruno K. Lino,Katia Pagnano,Rosane Bittencourt,Elenaide Nunes,Fabiola Traina,Lorena Figueiredo-Pontes,Armand Keating,Martin S. Tallman,Raul C. Ribeiro,Richard Dilon,Arnold Ganser,Miguel A. Sanz,Nancy Berliner,Peter Valk,Bob Löwenberg,Tiziana Ottone,Nelida I. Noguera,Maria T. Voso,Francesca Paoloni,Paola Fazi,Emanuele Ammatuna,Gerwin Huls,Jan Jacob Schuringa,Eduardo M. Rego,Antonio R. Lucena-Araujo |
| Affiliation: | 1. Department of Genetics, Federal University of Pernambuco, Recife, Brazil;2. Department of Genetics, Federal University of Pernambuco, Recife, Brazil Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil;3. Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil;4. Myeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK;5. Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil;6. Department of Internal Medicine, University of Pernambuco, Recife, Brazil;7. Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil;8. Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil;9. Hematology Division, Federal University of Paraná, Curitiba, Brazil;10. Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil;11. Princess Margaret Cancer Centre, Toronto, Ontario, Canada;12. Leukemia Service, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York City, New York, USA;13. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA;14. Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK;15. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;16. Department of Hematology, Valencia University Medical School, Valencia, Spain CIBERONC, Instituto Carlos III, Madrid, Spain;17. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA;18. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands;19. Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy;20. Santa Lucia Foundation, I.R.C.C.S., Neuro-Oncohematology, Rome, Italy;21. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA), GIMEMA Foundation, Rome, Italy;22. Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands;23. Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil |
| Abstract: | Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA. |
| Keywords: | anthracycline-based chemotherapy ATRA mtDNA content oxidative phosphorylation |