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ORIGINAL RESEARCH article

Front. Genet.

Sec. Cancer Genetics and Oncogenomics

This article is part of the Research TopicDeciphering molecular mechanisms behind tumor heterogeneity features by using nucleic acid-based technologiesView all 6 articles

Differentially Expressed Proteins in Plasma-Derived Extracellular Vesicles from Chronic Myeloid Leukemia Patients

Provisionally accepted
  • 1Instituto Carlos Chagas, Curitiba, Brazil
  • 2Universidade Federal do Parana, Curitiba, Brazil
  • 3Universidade de Sao Paulo, São Paulo, Brazil
  • 4Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil

The final, formatted version of the article will be published soon.

Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 fusion gene. Although tyrosine kinase inhibitors (TKIs) have transformed outcomes, treatment resistance persists. Plasma extracellular vesicles (EVs) reflect their cell of origin and may serve as stable biomarkers. To characterize the plasma EV proteome in CML patients with distinct treatment responses and T315I mutation status. EVs were isolated from the plasma of healthy controls (HC) and CML patients classified as good (GTR) or poor (PTR) treatment responders, treatment-free remission (TFR), and T315I or pre-T315I mutation carriers. EVs were purified by size-exclusion chromatography, characterized by NTA and TEM, and analyzed by label-free mass spectrometry, followed by differential expression, enrichment, and protein–protein interaction analyses. A total of 598 proteins were identified, 257 retained after quality and abundance filtering. Forty-two proteins were differentially expressed among HC, GTR, and PTR groups (p < 0.01), with PTR samples showing marked downregulation of cytoskeletal and chaperone proteins (such as MYH9, HSP90AB1, FERMT3). TFR patients exhibited distinct enrichment in complement and coagulation cascades (C3, C4B, F9, F11) and metabolic pathways. Plasma EV proteomes reflect CML clinical status, revealing immune and cytoskeletal alterations associated with treatment response, remission, and resistance, suggesting potential biomarkers for disease monitoring.

Keywords: biomarkers, Chronic myeloid leukemia, extracellular vesicles, Proteomics, T315I

Received: 06 Dec 2025; Accepted: 23 Jan 2026.

Copyright: © 2026 Kusma Wosniaki, Korte de Azevedo, Marin, Murillo Carrasco, Andrade, Brant, Batista, Bombardelli Gomig, Chammas, Aoki and Zanette. 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) or licensor 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.

* Correspondence: Dalila Lucíola Zanette

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