| Full text | |
| Author(s): Show less - |
de Almeida, Felipe Campos
;
Berzoti-Coelho, Maria G.
;
Toro, Diana Mota
;
Cacemiro, Maira da Costa
;
Bassan, Vitor Leonardo
;
Barretto, Gabriel Dessotti
;
Marques Garibaldi, Pedro Manoel
;
Palma, Leonardo Carvalho
;
De Figueiredo-Pontes, Lorena Lobo
;
Sorgi, Carlos Arterio
;
Faciolli, Lucia Helena
;
Gardinassi, Luiz Gustavo
;
de Castro, Fabiola Attie
Total Authors: 13
|
| Document type: | Journal article |
| Source: | FRONTIERS IN IMMUNOLOGY; v. 13, p. 8-pg., 2022-04-13. |
| Abstract | |
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. The efficacy of TKI is reduced in CML patients in the blastic phase-the most severe phase of the disease-and resistance to this drug has emerged. There is limited knowledge on the underlying mechanisms of disease progression and resistance to TKI beyond BCR-ABL1, as well as on the impact of TKI treatment and disease progression on the metabolome of CML patients. The present study reports the metabolomic profiles of CML patients at different phases of the disease treated with TKI. The plasma metabolites from CML patients were analyzed using liquid chromatography, mass spectrometry, and bioinformatics. Distinct metabolic patterns were identified for CML patients at different phases of the disease and for those who were resistant to TKI. The lipid metabolism in CML patients at advanced phases and TKI-resistant patients is reprogrammed, as detected by analysis of metabolomic data. CML patients who were responsive and resistant to TKI therapy exhibited distinct enriched pathways. In addition, ceramide levels were higher and sphingomyelin levels were lower in resistant patients compared with control and CML groups. Taken together, the results here reported established metabolic profiles of CML patients who progressed to advanced phases of the disease and failed to respond to TKI therapy as well as patients in remission. In the future, an expanded study on CML metabolomics may provide new potential prognostic markers for disease progression and response to therapy. (AU) | |
| FAPESP's process: | 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/21866-1 - Cytokine-mediated regulation of normal and neoplastic hematopoietic stem cells by natural killer cells |
| Grantee: | Lorena Lôbo de Figueiredo Pontes |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 18/19714-7 - Bone Marrow Mesenchymal Stromal Cells deregulation effect on BCR-ABL1-Myeloproliferative Neoplasms pathophysiology and progression |
| Grantee: | Fabíola Attié de Castro |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/23555-3 - Regulators microRNAs of HIPPO pathway in Chronic Myeloid Leukemia |
| Grantee: | Maria Gabriela Berzoti Coelho |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 15/00658-1 - New functional aspects of eicosanoids |
| Grantee: | Lúcia Helena Faccioli |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 18/01756-5 - Immunological and Functional Characterization of Multipotent Mesenchymal Stromal Cells in Myeloproliferative Neoplasms |
| Grantee: | Maira da Costa Cacemiro |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |