Comparative Mutational Profiling of Hematopoietic Progenitor Cells and Circulating Endothelial Cells (CECs) in Patients with Primary Myelofibrosis

oleh: Mirko Farina, Simona Bernardi, Nicola Polverelli, Mariella D’Adda, Michele Malagola, Katia Bosio, Federica Re, Camillo Almici, Andrew Dunbar, Ross L. Levine, Domenico Russo

Format: Article
Diterbitkan: MDPI AG 2021-10-01

Deskripsi

A role of endothelial cells (ECs) in Primary Myelofibrosis (PMF) was supposed since <i>JAK2</i> 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 <i>JAK2</i> mutation, together with <i>ABL1</i>, <i>IDH1</i>, <i>TET2</i> and <i>ASXL1</i>, <i>KMT2A</i>, respectively. 6 out of 8 shared only NON MPN-driver mutations: <i>TET2</i> and <i>NOTCH1</i> in one case; individual paired mutations in <i>TP53</i>, <i>KIT</i>, <i>SRSF2</i>, <i>NOTCH1</i> and <i>WT1</i>, 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 <i>JAK2V617F</i> 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.