TUMOR-DERIVED EXOSOMES MAY BE USED AS NEW INFORMATIVE TOOL FOR THE DETECTION OF BONE MARROW RESIDUAL CML LEUKEMIC CELLS ACTIVITY
Author(s): ,
Simona Bernardi
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy;Lab CREA,Spedali Civili di Brescia,Brescia,Italy
,
Chiara Foroni
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy;Lab CREA,Spedali Civili di Brescia,Brescia,Italy
,
Camilla Zanaglio
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy;Lab CREA,Spedali Civili di Brescia,Brescia,Italy
,
Federica Re
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy;Lab CREA,Spedali Civili di Brescia,Brescia,Italy
,
Nicola Polverelli
Affiliations:
Unit of Bone Marrow Transplantation,Spedali Civili di Brescia,Brescia,Italy
,
Alessandro Turra
Affiliations:
Unit of Bone Marrow Transplantation,Spedali Civili di Brescia,Brescia,Italy
,
Enrico Morello
Affiliations:
Unit of Bone Marrow Transplantation,Spedali Civili di Brescia,Brescia,Italy
,
Mirko Farina
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
,
Federica Cattina
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
,
Lisa Gandolfi
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
,
Tatiana Zollner
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
,
Eugenia Accorsi Buttini
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
,
Michele Malagola
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
Domenico Russo
Affiliations:
Unit of Bone Marrow Transplantation,University of Brescia,Brescia,Italy
EHA Library. Bernardi S. Jun 14, 2019; 266204; PF404
Dr. Simona Bernardi
Dr. Simona Bernardi
Contributions
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Abstract

Abstract: PF404

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Ph+ Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by BCR-ABL1 fusion-gene, derived from the t (9;22) translocation. Tyrosine Kinase Inhibitors (TKIs) target BCR-ABL1 protein, induce molecular response in the most of patients, prolong the survival and allow the treatment free remission. Many studies have demonstrated the persistence of leukemic cells in the bone marrow (BM) niche, even after treatment. The conventional minimal residual disease monitoring for CML patients is based on the RT-qPCR quantification of BCR-ABL1 transcript in the peripheral blood (PB) cells. However, it is not able to appreciate the activity of residual CML leukemic cells in the BM, responsible of the molecular relapse in the patients undergoing TKIs discontinuation. Exosomes, carrying different information of the cell of origin, have garnered considerable attention in cancer research thanks to the discovery of their messenger role in cellular communication. Moreover, there are some evidences regarding the possibility to isolate the different exosomes sub-populations targeting the antigens on their surface.

Aims
In this study we aimed to explore the feasibility of the tumor-derived exosomes fraction enrichment in CML patients in chronic phase (CP) and treated with TKIs. Ph- patients and healthy subjects served as controls.

Methods
BCR-ABL1 transcript was quantified following on PB cells both conventionally, according to the International Scale, and by dPCR, given the last published evidences of its accuracy and sensitivity. The exosomes enrichment was performed by a specific kit based on immuno-selection for a pan-cancer antigen. The quantification of BCR-ABL1exosomal transcript was performed by dPCR. In addition, Y4 transctript, an exosomal housekeeper, was quantified in order to assess the exosomal RNA quantity.

Results
The possibility of the tumor-derived exosomes enrichmentwas confirmed by the quantification of Y4 and the immuno-selection of the exosomes resulted specific thanks to the negative results obtained in healthy controls. In Ph-controls and in CML patients we were able to isolate tumor exosomes (Y4 positive). Moreover, the presence of BCR-ABL1 transcript in all CML exosomal samples highlighted, for the first time, the presence of active leukemic cells in CML patients in CP. 

 

Conclusion
These results suggest that tumor derived exosomes could be consider as a new toolfor the identification of active leukemic cells and for the assessment of an innovative monitoringfocused on the biological meaning of exosomes in CML.

Session topic: 7. Chronic myeloid leukemia - Biology & Translational Research

Keyword(s): BCR-ABL, Leukemia-associated antigen, MRD, PCR

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