Cargando…

Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors

Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in...

Descripción completa

Detalles Bibliográficos
Autores principales: Caocci, Giovanni, Deidda, Martino, Noto, Antonio, Greco, Marianna, Simula, Maria Pina, Mulas, Olga, Cocco, Daniele, Fattuoni, Claudia, Mercuro, Giuseppe, La Nasa, Giorgio, Cadeddu Dessalvi, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231160/
https://www.ncbi.nlm.nih.gov/pubmed/32326001
http://dx.doi.org/10.3390/jcm9041180
_version_ 1783535126921084928
author Caocci, Giovanni
Deidda, Martino
Noto, Antonio
Greco, Marianna
Simula, Maria Pina
Mulas, Olga
Cocco, Daniele
Fattuoni, Claudia
Mercuro, Giuseppe
La Nasa, Giorgio
Cadeddu Dessalvi, Christian
author_facet Caocci, Giovanni
Deidda, Martino
Noto, Antonio
Greco, Marianna
Simula, Maria Pina
Mulas, Olga
Cocco, Daniele
Fattuoni, Claudia
Mercuro, Giuseppe
La Nasa, Giorgio
Cadeddu Dessalvi, Christian
author_sort Caocci, Giovanni
collection PubMed
description Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in CML patients treated with TKIs. Methods: We investigated 39 adult CML patients in chronic-phase (mean age 49 years, range 24–70 years), with no comorbidities evidenced at baseline, who were consecutively identified with CML and treated with imatinib, nilotinib, dasatinib, and ponatinib. All patients performed Gas-Chromatography-Mass-Spectrometry-based metabolomic analysis and were divided into two groups (with and without CV-AEs). Results: Ten CV-AEs were documented. Seven CV-AEs were rated as 3 according to the Common Toxicity Criteria, and one patient died of a dissecting aneurysm of the aorta. The patients’ samples were clearly separated into two groups after analysis and the main discriminant metabolites were tyrosine, lysine, glutamic acid, ornithine, 2-piperdinecarboxylic acid, citric acid, proline, phenylalanine, threonine, mannitol, leucine, serine, creatine, alanine, and 4-hydroxyproline, which were more abundant in the CV-AE group. Conversely, myristic acid, oxalic acid, arabitol, 4-deoxy rithronic acid, ribose, and elaidic acid were less represented in the CV-AE group. Conclusions: CML patients with CV-AEs show a different metabolic profile, suggesting probable mechanisms of endothelial damage.
format Online
Article
Text
id pubmed-7231160
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72311602020-05-22 Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors Caocci, Giovanni Deidda, Martino Noto, Antonio Greco, Marianna Simula, Maria Pina Mulas, Olga Cocco, Daniele Fattuoni, Claudia Mercuro, Giuseppe La Nasa, Giorgio Cadeddu Dessalvi, Christian J Clin Med Article Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in CML patients treated with TKIs. Methods: We investigated 39 adult CML patients in chronic-phase (mean age 49 years, range 24–70 years), with no comorbidities evidenced at baseline, who were consecutively identified with CML and treated with imatinib, nilotinib, dasatinib, and ponatinib. All patients performed Gas-Chromatography-Mass-Spectrometry-based metabolomic analysis and were divided into two groups (with and without CV-AEs). Results: Ten CV-AEs were documented. Seven CV-AEs were rated as 3 according to the Common Toxicity Criteria, and one patient died of a dissecting aneurysm of the aorta. The patients’ samples were clearly separated into two groups after analysis and the main discriminant metabolites were tyrosine, lysine, glutamic acid, ornithine, 2-piperdinecarboxylic acid, citric acid, proline, phenylalanine, threonine, mannitol, leucine, serine, creatine, alanine, and 4-hydroxyproline, which were more abundant in the CV-AE group. Conversely, myristic acid, oxalic acid, arabitol, 4-deoxy rithronic acid, ribose, and elaidic acid were less represented in the CV-AE group. Conclusions: CML patients with CV-AEs show a different metabolic profile, suggesting probable mechanisms of endothelial damage. MDPI 2020-04-20 /pmc/articles/PMC7231160/ /pubmed/32326001 http://dx.doi.org/10.3390/jcm9041180 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caocci, Giovanni
Deidda, Martino
Noto, Antonio
Greco, Marianna
Simula, Maria Pina
Mulas, Olga
Cocco, Daniele
Fattuoni, Claudia
Mercuro, Giuseppe
La Nasa, Giorgio
Cadeddu Dessalvi, Christian
Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title_full Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title_fullStr Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title_full_unstemmed Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title_short Metabolomic Analysis of Patients with Chronic Myeloid Leukemia and Cardiovascular Adverse Events after Treatment with Tyrosine Kinase Inhibitors
title_sort metabolomic analysis of patients with chronic myeloid leukemia and cardiovascular adverse events after treatment with tyrosine kinase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231160/
https://www.ncbi.nlm.nih.gov/pubmed/32326001
http://dx.doi.org/10.3390/jcm9041180
work_keys_str_mv AT caoccigiovanni metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT deiddamartino metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT notoantonio metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT grecomarianna metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT simulamariapina metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT mulasolga metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT coccodaniele metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT fattuoniclaudia metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT mercurogiuseppe metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT lanasagiorgio metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors
AT cadeddudessalvichristian metabolomicanalysisofpatientswithchronicmyeloidleukemiaandcardiovascularadverseeventsaftertreatmentwithtyrosinekinaseinhibitors