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Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors

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 T...

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Autores principales: de Almeida, Felipe Campos, Berzoti-Coelho, Maria G., Toro, Diana Mota, Cacemiro, Maira da Costa, Bassan, Vitor Leonardo, Barretto, Gabriel Dessotti, Garibaldi, Pedro Manoel Marques, Palma, Leonardo Carvalho, de Figueiredo-Pontes, Lorena Lobo, Sorgi, Carlos Arterio, Faciolli, Lucia Helena, Gardinassi, Luiz Gustavo, de Castro, Fabíola Attié
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043757/
https://www.ncbi.nlm.nih.gov/pubmed/35493444
http://dx.doi.org/10.3389/fimmu.2022.840173
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author de Almeida, Felipe Campos
Berzoti-Coelho, Maria G.
Toro, Diana Mota
Cacemiro, Maira da Costa
Bassan, Vitor Leonardo
Barretto, Gabriel Dessotti
Garibaldi, Pedro Manoel Marques
Palma, Leonardo Carvalho
de Figueiredo-Pontes, Lorena Lobo
Sorgi, Carlos Arterio
Faciolli, Lucia Helena
Gardinassi, Luiz Gustavo
de Castro, Fabíola Attié
author_facet de Almeida, Felipe Campos
Berzoti-Coelho, Maria G.
Toro, Diana Mota
Cacemiro, Maira da Costa
Bassan, Vitor Leonardo
Barretto, Gabriel Dessotti
Garibaldi, Pedro Manoel Marques
Palma, Leonardo Carvalho
de Figueiredo-Pontes, Lorena Lobo
Sorgi, Carlos Arterio
Faciolli, Lucia Helena
Gardinassi, Luiz Gustavo
de Castro, Fabíola Attié
author_sort de Almeida, Felipe Campos
collection PubMed
description 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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spelling pubmed-90437572022-04-28 Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors de Almeida, Felipe Campos Berzoti-Coelho, Maria G. Toro, Diana Mota Cacemiro, Maira da Costa Bassan, Vitor Leonardo Barretto, Gabriel Dessotti Garibaldi, Pedro Manoel Marques Palma, Leonardo Carvalho de Figueiredo-Pontes, Lorena Lobo Sorgi, Carlos Arterio Faciolli, Lucia Helena Gardinassi, Luiz Gustavo de Castro, Fabíola Attié Front Immunol Immunology 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. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043757/ /pubmed/35493444 http://dx.doi.org/10.3389/fimmu.2022.840173 Text en Copyright © 2022 de Almeida, Berzoti-Coelho, Toro, Cacemiro, Bassan, Barretto, Garibaldi, Palma, de Figueiredo-Pontes, Sorgi, Faciolli, Gardinassi and de Castro https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
de Almeida, Felipe Campos
Berzoti-Coelho, Maria G.
Toro, Diana Mota
Cacemiro, Maira da Costa
Bassan, Vitor Leonardo
Barretto, Gabriel Dessotti
Garibaldi, Pedro Manoel Marques
Palma, Leonardo Carvalho
de Figueiredo-Pontes, Lorena Lobo
Sorgi, Carlos Arterio
Faciolli, Lucia Helena
Gardinassi, Luiz Gustavo
de Castro, Fabíola Attié
Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title_full Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title_fullStr Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title_full_unstemmed Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title_short Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
title_sort bioactive lipids as chronic myeloid leukemia’s potential biomarkers for disease progression and response to tyrosine kinase inhibitors
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043757/
https://www.ncbi.nlm.nih.gov/pubmed/35493444
http://dx.doi.org/10.3389/fimmu.2022.840173
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