| Autor: |
Coelho-Silva JL; 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., Silveira DRA; Hematology Division, LIM31, Faculdade de Medicina, University of São Paulo, São Paulo, SP, Brazil.; Department of Haematology, AC Camargo Cancer Centre, Sao Paulo, Brazil., Pereira-Martins DA; Center for Cell-Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil.; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Rojas CAO; Center for Cell-Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil., Lucena-Araujo AR; Department of Genetics, Federal University of Pernambuco, Recife, Brazil., Rego EM; Center for Cell-Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil.; Hematology Division, LIM31, Faculdade de Medicina, University of São Paulo, São Paulo, SP, Brazil., Machado-Neto JA; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Bendit I; Hematology Division, LIM31, Faculdade de Medicina, University of São Paulo, São Paulo, SP, Brazil., Rocha V; Hematology Division, LIM31, Faculdade de Medicina, University of São Paulo, São Paulo, SP, Brazil., Traina F; Department of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. ftraina@fmrp.usp.br.; Center for Cell-Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil. ftraina@fmrp.usp.br. |
| Abstrakt: |
Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62-93%]) and adverse (n = 71; 35% [17-61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26-81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes. |
