Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Bernardi, Simona; Farina, Mirko

doi:10.3390/biology10020105

Cited by 15 publications

(12 citation statements)

References 167 publications

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“…In oncohematology, exosomes have been mainly investigated in lymphoid malignancies, while the majority of the data about myeloid neoplasia are derived from limited in vitro studies. Little is known about real exosomes’ capability to serve as leukemic markers shuttling detectable mutated nucleic acids [ 6 ]. We previously reported the correlation between exosomal dsDNA concentrations and disease status in adult AMLs [ 25 ], and similar results were observed in pediatric AML patients [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Liquid biopsy has been widely explored in oncology and only lately has it been introduced in hematology, with a special focus on lymphoid malignancies [ 4 , 5 ]. Despite the presence of some in vitro data about the characterization of exosomes derived from myeloid leukemic cells, few studies have reported their investigation in patients affected by myeloid neoplasia [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

Bernardi

Farina

Bosio

et al. 2022

Cancers

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Exosomes are extracellular vesicles playing a pivotal role in the intercellular communication. They shuttle different cargoes, including nucleic acids from their cell of origin. For this reason, they have been studied as carriers of tumor markers in different liquid biopsy approaches, in particular for solid tumors. Few data are available concerning exosomes as markers of myeloid neoplasia. To better understand their real potential and the best approach to investigate leukemic exosomes, we present the results of a pilot feasibility study evaluating the application of next-generation sequencing analysis of dsDNA derived from exosomes isolated in 14 adult patients affected by acute myeloid leukemias. In particular, leukemia-derived exosome fractions have been analyzed. The concentration of dsDNA co-extracted with exosomes and the number and types of mutations detected were considered and compared with ones identified in the Bone Marrow (BM) and Peripheral Blood (PB) cells. Exosomal DNA concentration, both considering the cargo and the DNA surrounding the lipid membrane resulted in a linear correlation with leukemic burden. Moreover, exosomal DNA mutation status presented 86.5% of homology with BM and 75% with PB. The results of this pilot study confirmed the feasibility of a leukemia-derived exosome enrichment approach followed by exosomal dsDNA NGS analysis for AML biomarker detection. These data point to the use of liquid biopsy in myeloid neoplasia for the detection of active leukemic cells resident in the BM via a painless procedure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

Bernardi

Farina

Bosio

et al. 2022

Cancers

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“…Moreover, the high frequency of shared mutations in our cohort and the presence also of different mutations between the two cell subpopulations, make this hypothesis unlikely. Other possible mechanisms might be the fusion of mutated hematopoietic cell with an EC or the phagocytosis of cell-free DNA or extracellular vesicles [56,57], but they also seem very unlikely, considering the complexity and variability of the CECs molecular profile.…”

Section: Discussionmentioning

confidence: 99%

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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“…In addition, there have been reviews on topics similar to this review. But there is still a certain novelty in our paper ( 13 – 15 ). 1.…”

Section: Introductionmentioning

confidence: 91%

The Role of Exosomes in the Progression and Therapeutic Resistance of Hematological Malignancies

2022

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Exosomes are membrane limited structures which derive from cell membranes and cytoplasm. When released into extracellular space, they circulate through the extracellular fluid, including the peripheral blood and tissue fluid. Exosomes surface molecules mediate their targeting to specific recipient cells and deliver their contents to recipient cells by receptor-ligand interaction and/or phagocytosis and/or endocytosis or direct fusion with cell membrane. Exosomes contain many functional molecules, including nucleic acids (DNAs, mRNAs, non-coding RNAs), proteins (transcription factors, enzymes), and lipids which have biological activity. By passing these cargos, exosomes can transfer information between cells. In this way, exosomes are extensively involved in physiological and pathological processes, such as angiogenesis, matrix reprogramming, coagulation, tumor progression. In recent years, researcher have found that exosomes from malignant tumors can mediate information exchange between tumor cells or between tumor cells and non-tumor cells, thereby promoting tumor survival, progression, and resistance to therapy. In this review, we discuss the pro-tumor and anti-therapeutic effects of exosomes in hematological malignancies, hoping to contribute to the early conquest of hematological malignancy.

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Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Cited by 15 publications

References 167 publications

Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection

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

The Role of Exosomes in the Progression and Therapeutic Resistance of Hematological Malignancies

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