Comparative Mutational Profiling of Hematopoietic Progenitor Cells and Circulating Endothelial Cells (CECs) in Patients with Primary Myelofibrosis
Mirko Farina,
Simona Bernardi,
Nicola Polverelli,
Mariella D’Adda,
Michele Malagola,
Katia Bosio,
Federica Re,
Camillo Almici,
Andrew Dunbar,
Ross L. Levine,
Domenico Russo
Affiliations
Mirko Farina
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Simona Bernardi
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Nicola Polverelli
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Mariella D’Adda
Hematology Unit, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
Michele Malagola
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Katia Bosio
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Federica Re
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Camillo Almici
Laboratory for Stem Cells Manipulation and Cryopreservation, Department of Transfusion Medicine, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
Andrew Dunbar
Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Ross L. Levine
Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Domenico Russo
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
A role of endothelial cells (ECs) in Primary Myelofibrosis (PMF) was supposed since JAK2 mutation was found in endothelial precursor cells (EPCs) and in ECs captured by laser microdissection. By Cell Search method, the circulating endothelial cells (CECs) from 14 PMF patients and 5 healthy controls have been isolated and compared by NGS with CD34+Hematopoietic stem and progenitors cells (HSPCs) for panel of 54 myeloid-associated mutations. PMF patients had higher levels of CECs. No mutation was found in HSPCs and CECs from controls, while CECs from PMF patients presented several somatic mutations. 72% of evaluable patients shared at least one mutation between HSPCs and CECs. 2 patients shared the JAK2 mutation, together with ABL1, IDH1, TET2 and ASXL1, KMT2A, respectively. 6 out of 8 shared only NON MPN-driver mutations: TET2 and NOTCH1 in one case; individual paired mutations in TP53, KIT, SRSF2, NOTCH1 and WT1, in the other cases. In conclusion, 70% of PMF patients shared at least one mutation between HSPCs and CECs. These latter harbored several myeloid-associated mutations, besides JAK2V617F mutation. Our results support a primary involvement of EC in PMF and provide a new methodological approach for further studies exploring the role of the “neoplastic” vascular niche.
