Bioactive lipids as chronic myeloid leukemia’s potential biomarkers for disease progression and response to tyrosine kinase inhibitors
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2022
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Resumo
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.
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Chronic myeloid leukemia, Bioactive lipids, Tyrosine kinase inhibitors, Pathogenesis and metabolomics, Tyrosine kinasa inhibitor
Citação
ALMEIDA, Felipe Campos de et al. Bioactive lipids as chronic myeloid leukemia’s potential biomarkers for disease progression and response to tyrosine kinase inhibitors. Frontiers in Immunology, Lausanne, v. 13, e840173, 2022. DOI: 10.3389/fimmu.2022.840173. Disponível em: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.840173/full. Acesso em: 28 jan. 2025.