Blood and endothelial cells: together through thick and thin

Teofili, Luciana; Larocca, Luigi Maria

doi:10.1182/blood-2012-11-467795

Cited by 3 publications

(6 citation statements)

References 8 publications

(3 reference statements)

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“…Here we show that 4 out of 5 (80%) evaluable patients with JAK2 V617F MPN‐neg harbour the JAK2 V617F mutation in BM‐derived E‐CFC. While the detection of JAK2 V617F in PB is a well‐established risk factor for BCS and the presence of JAK2 V617F ‐positive EC has been implicated in the pathogenesis of thrombosis in patients with JAK2 V617F MPN (Sozer et al , ; Teofili & Larocca, ), the presence of JAK2 V617F ‐positive E‐CFC has not been reported before in JAK2 V617F MPN‐neg patients. Although the number of patients analysed in our study is small, we found a higher incidence of JAK2 V617F ‐positive E‐CFC in JAK2 V617F MPN‐neg when compared to a previous study of patients with JAK2 V617F MPN (Teofili et al , ).…”

Section: Demographic Features Of Bcs Patients and Jak2v617f Allele‐bumentioning

confidence: 99%

Granulocyte whole exome sequencing and endothelial JAK2V617F in patients with JAK2V617F positive Budd‐Chiari Syndrome without myeloproliferative neoplasm

et al. 2016

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Section: Demographic Features Of Bcs Patients and Jak2v617f Allele‐bumentioning

confidence: 99%

Granulocyte whole exome sequencing and endothelial JAK2V617F in patients with JAK2V617F positive Budd‐Chiari Syndrome without myeloproliferative neoplasm

et al. 2016

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“…Regardless of the existence or not of a common precursor, the presence of somatic mutations in ECs may have important consequences in the disease development and the insurgence of vascular complications in PMF patients. Indeed, mutated ECs in PMF may represent a "neoplastic" vascular niche, which allow blood cells adhesion, vascular complications and the tumor cell growth, as demonstrated for JAK2 -mutated ECs using in vitro and in vivo assays [14,[58][59][60][61][62]. A longer follow up of our patients and new studies investigating the "neoplastic" vascular niche in humans are needed to validate this hypothesis.…”

Section: Discussionmentioning

confidence: 77%

“…Some authors have tried to answer these questions by looking at the JAK2 MPN driver mutation in EPCs [16][17][18]23,24] or mature ECs captured by laser microdissection [21,25]. Overall, the results of these studies suggest an hypothetical direct ECs involvement in PMF pathogenesis [13,14]. However, difficulties in evaluating the "true" EPC or the limitations in studying "in vivo" mature ECs do not permit the clear demonstration of the endothelium implication in PMF.…”

Section: Discussionmentioning

confidence: 99%

“…Characteristically, PMF patients also present with a higher rate of vascular complications [8][9][10] and increased BM and spleen vascularity [11]. Considering these features and the physiological role of JAK-STAT pathway in preserving the endothelial-vascular homeostasis [12], it has been supposed that endothelial cells (ECs) have a role in the pathogenesis of PMF and other MPNs [13,14]. To explore this hypothesis, some studies have investigated the presence of JAK2 V617F mutation in MPN patients' ECs and its role as predictor of thrombosis [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Considering these features and the physiological role of JAK-STAT pathway in preserving the endothelial-vascular homeostasis [12], it has been supposed that endothelial cells (ECs) have a role in the pathogenesis of PMF and other MPNs [13,14]. To explore this hypothesis, some studies have investigated the presence of JAK2 V617F mutation in MPN patients' ECs and its role as predictor of thrombosis [13][14][15]. Unfortunately, the results of these studies are discordant.…”

Section: Introductionmentioning

confidence: 99%

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

Farina

Bernardi

Polverelli

et al. 2021

Cells

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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.

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The possible role of mutated endothelial cells in myeloproliferative neoplasms

2021

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Myeloproliferative neoplasms (MPN) are chronic, clonal hematologic malignancies characterized by myeloproliferation and a high incidence of vascular complications (thrombotic and bleeding). Although MPN-specific driver mutations have been identified, the underlying events that culminate in these clinical manifestations require further clarification. We reviewed the numerous studies performed during the last decade identifying endothelial cell (EC) dysregulation as a factor contributing to MPN disease development. The JAK2V617F MPN mutation and other myeloid-associated mutations have been detected not only in hematopoietic cells but also in EC and their precursors in MPN patients, suggesting a link between mutated EC and the high incidence of vascular events. To date, however, the role of EC in MPN continues to be questioned by some investigators. In order to further clarify the role of EC in MPN, we first describe the experimental strategies used to study EC biology and then analyze the available evidence generated using these assays which implicate mutated EC in MPN-associated abnormalities. Mutated EC have been reported to possess a pro-adhesive phenotype as a result of increased endothelial Pselectin exposure, secondary to degranulation of Weibel-Palade bodies, which is further accentuated by exposure to pro-inflammatory cytokines. Additional evidence indicates that MPN myeloproliferation requires JAK2V617F expression by both hematopoietic stem cells and EC. Furthermore, the reports of JAK2V617F and other myeloid malignancy- associated mutations in both hematopoietic cells and EC in MPN patients support the hypothesis that MPN driver mutations may first appear in a common precursor cell for both EC and hematopoietic cells.

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Blood and endothelial cells: together through thick and thin

Cited by 3 publications

References 8 publications

Granulocyte whole exome sequencing and endothelial JAK2V617F in patients with JAK2V617F positive Budd‐Chiari Syndrome without myeloproliferative neoplasm

Granulocyte whole exome sequencing and endothelial JAK2V617F in patients with JAK2V617F positive Budd‐Chiari Syndrome without myeloproliferative neoplasm

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

The possible role of mutated endothelial cells in myeloproliferative neoplasms

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