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Metabolic shift of chronic myeloid leukemia patients under imatinib-pioglitazone regimen and discontinuation.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2021 Jul 24; Vol. 38 (9), pp. 100. Date of Electronic Publication: 2021 Jul 24. - Publication Year :
- 2021
-
Abstract
- The Estudo de Descontinuação de Imatinibe após Pioglitazona (EDI-PIO) is a single-center, longitudinal, prospective, phase 2, non-randomized, open, clinical trial (NCT02852486, August 2, 2016 retrospectively registered) for the discontinuation of imatinib after concomitant use of pioglitazone, being the first of its kind in a Brazilian population with chronic myeloid leukemia. Due to remaining of leukemic quiescent cells that are not affected by tyrosine kinase inhibitors, it has been suggested the use of pioglitazone, a PPARγ agonist, together with imatinib as a strategy for the maintenance of deep molecular response. The clinical benefit to this association is still controversial, and the metabolic alteration along this process remains unclear. Therefore, we applied a metabolomic protocol using high-resolution mass spectrometry to profile plasmatic metabolic response of a prospective cohort of ten individuals under discontinuation of imatinib and pioglitazone protocol. By comparing patients under pioglitazone and imatinib treatment with imatinib monotherapy and discontinuation phase, we were able to annotate 41 and 36 metabolites, respectively. The metabolic alterations observed during imatinib-pioglitazone combined therapy are associated with an extensive lipid remodeling, with activation of β-oxidation pathway, in addition to the presence of markers that suggest mitochondrial dysfunction.<br /> (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Adult
Aged
Female
Follow-Up Studies
Humans
Imatinib Mesylate administration & dosage
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Longitudinal Studies
Male
Metabolic Diseases chemically induced
Metabolic Diseases metabolism
Middle Aged
Non-Randomized Controlled Trials as Topic
Pioglitazone administration & dosage
Prognosis
Prospective Studies
Retrospective Studies
Young Adult
Antineoplastic Combined Chemotherapy Protocols adverse effects
Biomarkers, Tumor metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Metabolic Diseases pathology
Metabolome
Withholding Treatment
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 38
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 34302533
- Full Text :
- https://doi.org/10.1007/s12032-021-01551-5