Circulating microvesicles are less procoagulant and carry different miRNA cargo in myelodysplasia

Enjeti, Anoop K; Ariyarajah, Anita; D'Crus, Angel; Riveros, Carlos; Seldon, Michael; Lincz, Lisa F.

doi:10.1016/j.bcmd.2018.11.001

Cited by 9 publications

(13 citation statements)

References 23 publications

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“…In MDS plasma, we did not identify higher numbers of EVs but rather noticed differences in their sizes, specifically a particular increase in EVs of larger diameters and a higher content of their RNA cargo (SI 5). This is in agreement with a previous study showing that the RNA content was doubled in MDS compared to controls [19]. Thus, functional studies investigating reasons of this increase and its relation to MDS pathogenesis are needed.…”

Section: Discussionsupporting

confidence: 92%

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Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

Hruštincová

Krejčík

Kundrat

et al. 2020

Cells

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Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.

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Section: Discussionsupporting

confidence: 92%

“…Giudice et al [18] examined the possible diagnostic and prognostic potential of plasma exosomal miRNAs and found 21 miRNAs that had a strong association with MDS. Finally, Enjeti et al [19] studied the sncRNA content in EVs of MDS patients and revealed that their cargo was approximately twice as high as that in EVs of the healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

Hruštincová

Krejčík

Kundrat

et al. 2020

Cells

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“…described a significantly higher plasma MV expression in AML patients compared to healthy controls 9 ; Enjety et al . reported that MV size distribution did not differ significantly between MDS and normal samples 10 . Hrustincova et al .…”

Section: Figurementioning

confidence: 95%

“…8 Szczepanski et al described a significantly higher plasma MV expression in AML patients compared to healthy controls 9 ; Enjety et al reported that MV size distribution did not differ significantly between MDS and normal samples. 10 Hrustincova et al found no association between particle counts or cumulative volume and MDS. 11 Serum exosomes were evaluated for the surface markers CD13, CD33, CD117, CD34, HLA-DR, CD38, CD11b, CD105, and CD133 by flow cytometry using the Submicron Bead Calibration kit (microbead diameter, 200-500-800 nm; Bangs Laboratories, Fishers, IN, USA) to identify the exosome gate.…”

mentioning

confidence: 95%

The exosomal surface phenotype and inflamma‐miR cargo correlate with MDS diagnosis

et al. 2020

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“…Considering the limitations with regard to their comparability, special efforts were invested on liquid biopsies by analysis of free and MV-bound miRNAs from total blood, serum, and plasma. Using this approach, a higher miRNA content in MV of MDS patients compared to healthy controls was found [ 93 ] suggesting that the miRNA cargo of circulating MVs may contribute to the pathophysiology of this disease. Furthermore, the miRNA content differs between total plasma and EVs in MDS versus healthy controls [ 84 ].…”

Section: Mirna Expression In Mds and Samlmentioning

confidence: 99%

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Bauer

Vaxevanis

Heimer

et al. 2020

IJMS

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Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

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Circulating microvesicles are less procoagulant and carry different miRNA cargo in myelodysplasia

Cited by 9 publications

References 23 publications

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

The exosomal surface phenotype and inflamma‐miR cargo correlate with MDS diagnosis

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

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