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

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

doi:10.3390/cells10102764

Cited by 10 publications

(6 citation statements)

References 68 publications

(118 reference statements)

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“…These findings appear to confirm the origin of PMF as multipotent CD34+ HPSCs. The most frequent mutations concern driver genes such as JAK2 and non-driver genes such as ASXL1 , IDH1/2 , SRSF2 , EZH1 [ 41 ]. Further studies confirm a similar mutational profile in circulating free DNA (cfDNA) and in paired granulocyte DNA obtained from the plasma of PMF patients [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis

Visani¹,

Etebari

Fuligni

et al. 2023

Cancers

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Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow sclerosis, extra-medullary hematopoiesis, and possible transformation to acute leukemia. In the last decade, the molecular pathogenesis of the disease has been largely uncovered. Particularly, genetic and genomic studies have provided evidence of deregulated oncogenes in PMF as well as in other MPNs. However, the mechanisms through which transformation to either the myeloid or lymphoid blastic phase remain obscure. Particularly, it is still debated whether the disease has origins in a multi-potent hematopoietic stem cells or instead in a commissioned myeloid progenitor. In this study, we aimed to shed light upon this issue by using next generation sequencing (NGS) to study both myeloid and lymphoid cells as well as matched non-neoplastic DNA of PMF patients. Whole exome sequencing revealed that most somatic mutations were the same between myeloid and lymphoid cells, such findings being confirmed by Sanger sequencing. Particularly, we found 126/146 SNVs to be the e same (including JAK2V617F), indicating that most genetic events likely to contribute to disease pathogenesis occurred in a non-commissioned precursor. In contrast, only 9/27 InDels were similar, suggesting that this type of lesion contributed instead to disease progression, occurring at more differentiated stages, or maybe just represented “passenger” lesions, not contributing at all to disease pathogenesis. In conclusion, we showed for the first time that genetic lesions characteristic of PMF occur at an early stage of hematopoietic stem cell differentiation, this being in line with the possible transformation of the disease in either myeloid or lymphoid acute leukemia.

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Section: Discussionmentioning

confidence: 99%

Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis

Visani¹,

Etebari

Fuligni

et al. 2023

Cancers

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“…Farina et al aimed to isolate CECs in primary myelofibrosis patients to compare their mutation spectrum with blood cells from the same individuals. They discovered the JAK2 mutation in a subset of patients' CECs and identified common myeloid-associated mutations between CECs and haematopoietic stem and progenitor cells, including ASXL1, TET2, and SRSF2 [52,53]. However, these findings are limited by the small patient cohort and the low sensitivity of the next generation sequencing method.…”

Section: Circulating Endothelial Cells and Cancer Diseasesmentioning

confidence: 99%

Circulating endothelial cells in pathophysiology

Brett,

Dignat George,

James

2024

Current Opinion in Hematology

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Purpose of review The purpose of this review is to synthesize recent insights into the roles and importance of circulating endothelial cells (CECs) as indicators of the severity, progression, and prognosis of vascular-related diseases. Recent findings Recent studies have identified elevated counts of CECs in pathological conditions, notably inflammatory or cardiovascular diseases such as acute myocardial infarction and heart failure, underscoring their potential as sensitive indicators of disease. Furthermore, the rise in CEC levels in cancer patients, particularly with disease advancement, points to their role in cancer-associated angiogenesis and response to treatment. Summary This review underscores the evolving significance of CECs as markers for evaluating the gravity and advancement of diseases with vascular injury, including cardiovascular diseases, cancer, inflammatory conditions, and thromboembolic events. These last years, efforts made to standardize flow cytometry detection of CEC and the development of highly sensitive techniques to isolate, quantify or phenotype rare cells open promising avenues for clinical application. This may yield extensive knowledge regarding the mechanisms by which endothelial cells contribute to a variety of vascular-related disorders and their clinical value as emerging biomarkers

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“…Starting from this hypothesis, a recent study compared the mutational profiles of hematopoietic progenitor cells and circulating endothelial cells in patients with PMF. It showed that the JAK2 mutation is present in both cell populations, suggesting that endothelial circulating cells could play an important role in the pathogenesis and progression of PMF, as well as the associated vascular complications [21].…”

Section: The Link Between Mpd and Choreamentioning

confidence: 99%

Chorea and Cognitive Impairment in JAK2V617F-Positive Myeloproliferative Disorders: A Case Report and Literature Review

Butnariu,

Antonescu-Ghelmez,

Moraru

et al. 2023

Medicina

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Chorea is a hyperkinetic movement disorder, accompanied by dystonia, myoclonus, tics, stereotypies, and tremors. It is characterized by excessive, purposeless movements that are distressing, irregularly timed, and randomly distributed. Chorea can be present in many diseases, such as hereditary, metabolic disturbance, drug-induced, and functional disorders, and, rarely, genetic, autoimmune, and infectious diseases. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that leads to ineffective clonal hematopoiesis, fibrous tissue deposits in the bone marrow, extramedullary hematopoiesis, and splenomegaly. In rare cases, following uncertain pathological mechanisms, it can present with chorea, particularly affecting the limbs, head, and orofaciolingual muscles. We present a case of a male patient with evolving PMF over several years who was admitted for progressive cognitive impairment and generalized involuntary movement disorder. We also present a review of all cases of myeloproliferative disorders presenting with chorea published in the last 40 years.

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

Cited by 10 publications

References 68 publications

Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis

Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis

Circulating endothelial cells in pathophysiology

Chorea and Cognitive Impairment in JAK2V617F-Positive Myeloproliferative Disorders: A Case Report and Literature Review

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