Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia
| Autor: | Enrico Morello, Michele Malagola, Federica Cattina, Chiara Foroni, Federica Re, Domenico Russo, Simona Bernardi, Tatiana Zollner, Eugenia Accorsi Buttini, Nicola Polverelli, Lisa Gandolfi, Camilla Zanaglio, Mirko Farina, Alessandro Turra |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Fusion Proteins bcr-abl exosomes Biology Exosome Disease-Free Survival 03 medical and health sciences 0302 clinical medicine chronic myeloid leukemia Bone Marrow Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Internal medicine Genetics medicine Humans Protein Kinase Inhibitors Aged Aged 80 and over Hematology digital PCR Myeloid leukemia Articles General Medicine Middle Aged Cell cycle medicine.disease Microvesicles minimal residual disease monitoring Leukemia 030104 developmental biology medicine.anatomical_structure Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Feasibility Studies Female Bone marrow Tyrosine kinase |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2019.4372 |
| Popis: | Due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the break-point cluster region-proto-oncogene 1 tyrosine-protein kinase (BCR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BCR-ABL1 protein and induce major or deep molecular responses in the majority of patients. Despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render CML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (CP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PCR (dPCR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BCR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in CML. |
| Databáze: | OpenAIRE |
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