Implication of microRNAs in the Pathogenesis of MDS

Fang, Jing; Varney, Melinda E.; Starczynowski, Daniel T.

doi:10.2174/1381612811209023170

Cited by 20 publications

(16 citation statements)

References 106 publications

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“…It has been previously published that miR10-a and miR15-a are overexpressed in hematopoietic cells from MDS patients[ 24 ]. In Fig 2 we can observe that these two microRNAs are among the most expressed in MVs from our patients and they were selected to assess if their expression was modified in CD34 + cells.…”

Section: Resultsmentioning

confidence: 99%

“…MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have a crucial role in the regulation of hematopoiesis[ 35 ]. MicroRNAs can play a role in the development of some malignant hematopoietic disorders such as MDS[ 24 ]. Evidence that microRNAs deregulation in the microenvironment is involved in MDS pathogenesis comes from the seminal study of Raaijmaikers et al[ 9 ], who demonstrated that, when DICER-1 was deleted in murine osteoprogenitors, these animals developed an MDS similar to the human disease.…”

Section: Discussionmentioning

confidence: 99%

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Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients

et al. 2016

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Exosomes/microvesicles (MVs) provide a mechanism of intercellular communication. Our hypothesis was that mesenchymal stromal cells (MSC) from myelodysplastic syndrome (MDS) patients could modify CD34+ cells properties by MVs. They were isolated from MSC from MDS patients and healthy donors (HD). MVs from 30 low-risk MDS patients and 27 HD were purified by ExoQuick-TC™ or ultracentrifugation and identified by transmission electron microscopy, flow cytometry (FC) and western blot for CD63. Incorporation of MVs into CD34+ cells was analyzed by FC, and confocal and fluorescence microscopy. Changes in hematopoietic progenitor cell (HPC) properties were assessed from modifications in microRNAs and gene expression in CD34+ cells as well as viability and clonogenic assays of CD34+ cells after MVs incorporation. Some microRNAs were overexpressed in MVs from patients MSC and two of them, miR-10a and miR-15a, were confirmed by RT-PCR. These microRNAs were transferred to CD34+ cells, modifying the expression of MDM2 and P53 genes, which was evaluated by RT-PCR and western blot. Finally, examining CD34+ cells properties after incorporation, higher cell viability (p = 0.025) and clonogenic capacity (p = 0.037) were observed when MVs from MDS patients were incorporated. In summary, we show that BM-MSC release MVs with a different cargo in MDS patients compared with HD. These structures are incorporated into HPC and modify their properties.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients

et al. 2016

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“…3,5 U literaturi se genska ekspresija miRNK dovodi u vezu s dijagnozom, klasifikacijom i progresijom raz ličitih bolesti: B-kroničnom limfocitnom leukemijom (B-KLL), 6 karcinomom pluća, 7 hepatocelularnim karcinomom, 8 akutnom mijeloičnom leukemijom (AML). 9 Istraživanja miRNK u MDS-u relativno su rijetka, većina ih je usmjerena na višestruko profiliranje različitih miRNK, a tek nekoliko na patogenezu i nastanak MDS-a s kojim se u vezu dovode snižene razine genskih ekspresija specifičnih miRNK hsa-miR--146a, hsa-miR-150, let-7e, hsa-miR-23a, hsa-miR--103, hsa miR-126. [10][11][12] Povišenu razinu genske ekspresije miRNK hsa-miR-125b u MDS-u opisali su 2008. godine Bousquet i suradnici.…”

Section: Discussionunclassified

EXPRESSION OF micro RNAs (miRNAs) IN MYELODYSPLASTIC SYNDROME (MDS)

Paro

Rogulj

Kaić

et al. 2019

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Myelodisplasia or myelodysplastic syndrome (MDS) is the name for a group of heterogeneous clonal hematological disorders of hematopoietic stem cells followed by ineffective hematopoesis of one or more cell lines and the emergence of consequent cytopenias with increased risk of progression to acute myelogenous leukemia (AML). Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding RNA molecules that, apart from contributing to MDS pathogenesis, act as regulators of epigenetic mechanisms and also are recognized as potential prognostic markers for early diagnosis and classification of MDS. The aim of the study was to examine the levels of gene expression of specific miRNAs (hsa-miR-125a, hsa-miR-99b, hsa-miR-126 and hsa-miR-125b) in healthy volunteers plasma and MDS diagnosed patients. Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of four healthy volunteers and 33 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. Statistically significant difference in gene expression of miRNA in healthy volunteers compared to the MDS patients was not found (P [hsa-miR-125a] = 0.398; P [hsa-miR-99b] = 0.134; P [hsa- miR-126] = 0.305; P [hsa-miR-125b] = 0.079). MiRNA ratios of hsa-miR-125a and hsa-miR-99b in MDS patients were almost twice as high compared to normalized levels of gene expression in healthy volunteers (2.30 versus 1.90), and the level of change of miRNAs hsa-miR-125 and hsa-miR-99b was more than two times higher than the level of change of miRNA hsa-miR-125b. Finally, the results of the research indicate that the gene expression of miRNAs hsa-miR-125a and hsa-miR-99b could be regulated by the same mechanism and could be clinically relevant in MDS patients.

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“…12 Not only have these coding gene mutations been linked to disease progression and prognosis in MDSs, [13][14][15][16][17] but dysregulation of noncoding RNAs, such as the microRNAs, have also been implicated as important elements in the pathogenesis and disease evolution of MDSs. [18][19][20][21] Recent research works have revealed that the long noncoding RNAs (lncRNAs), a novel class of versatile noncoding RNAs operationally defined as transcripts longer than 200 nucleotides, play crucial roles in a constellation of biological processes including chromatin modification, regulation of gene expression in various signaling pathways, genomic imprinting, and epigenetic control. [22][23][24][25] Although a myriad of previous publications have established the association between deranged lncRNA expression and carcinogenesis, tumor progression, and metastasis in a wide variety of solid cancers, [26][27][28][29][30][31][32][33] relatively limited data exist so far on how these lncRNAs are involved in normal and malignant hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes

Yao

Chen

Huang³

et al. 2017

Blood Advances

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Key Points• Through lncRNA profiling, we identified an MDS patient subset with distinct clinical and mutational patterns along with inferior outcomes.• A concise yet powerful 4-lncRNA risk-scoring system was devised with the potential to improve current MDS risk stratification.Long noncoding RNAs (lncRNAs) not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in myelodysplastic syndromes (MDSs) remains unclear to date. In this study, we profiled lncRNA expressions in 176 adult patients with primary MDS, and identified 4 lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk-scoring system with the weighted sum of these 4 lncRNAs. Higher lncRNA scores were associated with higher marrow blast percentages, higher-risk subtypes of MDSs (based on both the Revised International Prognostic Scoring System [IPSS-R] and WorldHealth Organization classification), complex cytogenetic changes, and mutations in RUNX1, ASXL1, TP53, SRSF2, and ZRSR2, whereas they were inversely correlated with SF3B1 mutation. Patients with higher lncRNA scores had a significantly shorter OS and a higher 5-year leukemic transformation rate compared with those with lower scores. The prognostic significance of our 4-lncRNA risk score could be validated in an independent MDS cohort. In multivariate analysis, higher lncRNA scores remained an independent unfavorable risk factor for OS (relative risk, 4.783; P , .001) irrespective of age, cytogenetics, IPSS-R, and gene mutations. To our knowledge, this is the first report to provide a lncRNA platform for risk stratification of MDS patients. In conclusion, our integrated 4-lncRNA risk-scoring system is correlated with distinctive clinical and biological features in MDS patients, and serves as an independent prognostic factor for survival and leukemic transformation. This concise yet powerful lncRNA-based scoring system holds the potential to improve the current risk stratification of MDS patients.

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Implication of microRNAs in the Pathogenesis of MDS

Cited by 20 publications

References 106 publications

Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients

Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients

EXPRESSION OF micro RNAs (miRNAs) IN MYELODYSPLASTIC SYNDROME (MDS)

A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes

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