A 4-gene prognostic index for enhancing acute myeloid leukaemia survival prediction.

Autor: Ortiz Rojas CA; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil.; Center for Cell-Based Therapy, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Pereira-Martins DA; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil.; Center for Cell-Based Therapy, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Bellido More CC; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Sternadt D; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Weinhäuser I; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil.; Center for Cell-Based Therapy, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Hilberink JR; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Coelho-Silva JL; Center for Cell-Based Therapy, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Thomé CH; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil., Ferreira GA; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil., Ammatuna E; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Huls G; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Valk PJ; Erasmus University Medical Center, Rotterdam, The Netherlands., Schuringa JJ; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Rego EM; Hematology Division, Department of Internal Medicine, Laboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil.; Center for Cell-Based Therapy, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Jun; Vol. 204 (6), pp. 2287-2300. Date of Electronic Publication: 2024 Apr 23.
DOI: 10.1111/bjh.19472
Abstrakt: Despite advancements in utilizing genetic markers to enhance acute myeloid leukaemia (AML) outcome prediction, significant disease heterogeneity persists, hindering clinical management. To refine survival predictions, we assessed the transcriptome of non-acute promyelocytic leukaemia chemotherapy-treated AML patients from five cohorts (n = 975). This led to the identification of a 4-gene prognostic index (4-PI) comprising CYP2E1, DHCR7, IL2RA and SQLE. The 4-PI effectively stratified patients into risk categories, with the high 4-PI group exhibiting TP53 mutations and cholesterol biosynthesis signatures. Single-cell RNA sequencing revealed enrichment for leukaemia stem cell signatures in high 4-PI cells. Validation across three cohorts (n = 671), including one with childhood AML, demonstrated the reproducibility and clinical utility of the 4-PI, even using cost-effective techniques like real-time quantitative polymerase chain reaction. Comparative analysis with 56 established prognostic indexes revealed the superior performance of the 4-PI, highlighting its potential to enhance AML risk stratification. Finally, the 4-PI demonstrated to be potential marker to reclassified patients from the intermediate ELN2017 category to the adverse category. In conclusion, the 4-PI emerges as a robust and straightforward prognostic tool to improve survival prediction in AML patients.
(© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: