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 breakpoint 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.

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Bernardi, Simona
;
FORONI, Chiara;Zanaglio, Camilla;Re, Federica;Polverelli, Nicola;Turra, Alessandro;Morello, Enrico;Farina, Mirko;Cattina, Federica;Gandolfi, Lisa;ZOLLNER, TATIANA;ACCORSI BUTTINI, EUGENIA;Malagola, Michele;Russo, Domenico
2019

Abstract

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 breakpoint 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/525512
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