Comparative mutational profiling of hematopoietic progenitor cells and circulating endothelial cells (CECs) in patients with primary myelofibrosis Journal Article
| Authors: | Farina, M.; Bernardi, S.; Polverelli, N.; D’Adda, M.; Malagola, M.; Bosio, K.; Re, F.; Almici, C.; Dunbar, A.; Levine, R. L.; Russo, D. |
| Article Title: | Comparative mutational profiling of hematopoietic progenitor cells and circulating endothelial cells (CECs) in patients with primary myelofibrosis |
| Abstract: | 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | adult; clinical article; controlled study; aged; myelofibrosis; gene mutation; human cell; overall survival; somatic mutation; janus kinase 2; myeloid metaplasia; molecular genetics; polymerase chain reaction; neoplasm; cd34 antigen; stem cell factor receptor; immunofluorescence; abelson kinase; mutational analysis; protein p53; genetic susceptibility; splenomegaly; endoglin; hematopoiesis; hematopoietic stem cell; leukocyte count; wt1 protein; dna extraction; notch1 receptor; microdissection; histone lysine methyltransferase; isocitrate dehydrogenase 1; blood culture; cd146 antigen; mixed lineage leukemia protein; high throughput sequencing; human; male; female; article; whole exome sequencing; serine arginine rich splicing factor; receptor type tyrosine protein phosphatase c; vascular biology; circulating endothelial cells; hematopoiesis-stem and primitive progenitor cells; vascular biology-endothelial cells; circulating endothelial cell |
| Journal Title: | Cells |
| Volume: | 10 |
| Issue: | 10 |
| ISSN: | 2073-4409 |
| Publisher: | MDPI |
| Date Published: | 2021-10-01 |
| Start Page: | 2764 |
| Language: | English |
| DOI: | 10.3390/cells10102764 |
| PROVIDER: | scopus |
| PMCID: | PMC8534986 |
| PUBMED: | 34685741 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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