Metabolic shift of chronic myeloid leukemia patients under imatinib-pioglitazone regimen and discontinuation

Author(s)

Oliveira Povoa, Valquiria Mariane ^{[1, 2]} ; Delafiori, Jeany ^[2] ; Dias-Audibert, Flavia Luisa ^[2] ; de Oliveira, Arthur Noin ^[2] ; Pascoal Lopes, Ana Beatriz ^[1] ; de Paula, Erich Vinicius ^[1] ; Barbosa Pagnano, Katia Borgia ^[1] ; Catharino, Rodrigo Ramos ^[2]

Affiliation

^[1] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Innovare Biomarkers Lab, Sch Pharmaceut Sci, Campinas, SP - Brazil

• Document type: Journal article
• Source: MEDICAL ONCOLOGY; v. 38, n. 9 SEP 2021.
• Web of Science Citations: 0

Abstract

The Estudo de Descontinuacao de Imatinibe apos 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 PPAR gamma 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 beta-oxidation pathway, in addition to the presence of markers that suggest mitochondrial dysfunction. {[}GRAPHICS] . (AU)

• FAPESP's process: 19/05718-3 - Determination of metabolic alterations and therapeutic potential of Zika Virus in cancer cells by mass spectrometry and artificial intelligence
• Grantee: Jeany Delafiori
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)