MicroRNA expression profile in granulocytes from primary myelofibrosis patients

Guglielmelli, Paola; Tozzi, Lorenzo; Pancrazzi, Alessandro; Bogani, Costanza; Antonioli, Elisabetta; Ponziani, Vanessa; Poli, Giada; Zini, Roberta; Ferrari, Sérgio; Manfredini, Rossella; Bosi, Alberto; Vannucchi, Alessandro M.

doi:10.1016/j.exphem.2007.08.020

Cited by 71 publications

(70 citation statements)

References 60 publications

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“…Deregulated miRNA profiles have been reported in MPN patients during in vitro erythroid differentiation as well as in peripheral blood granulocytes, platelets, and reticulocytes [26,27]. Since the MPNs are stem cell disorders, comprehensive miRNA analysis in MPN stem cells is needed to further delineate their roles in MPN pathogenesis but so far there is only limited data in this area [26,[28][29][30].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

Zhan

Cardozo

et al. 2013

Blood Cells, Molecules, and Diseases

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Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2 V617F mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2 V617F -positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.

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Section: Introductionmentioning

confidence: 99%

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

Zhan

Cardozo

et al. 2013

Blood Cells, Molecules, and Diseases

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“…So far, all our knowledge on miRNA expression in Ph − MPN is based on analyses of in vitro-differentiated cells and peripheral blood cells [4][5][6]. In this approach, we have analysed for the first time, a subset of miRNA from bone marrow cells and megakaryocytes in normal haematopoiesis and in Ph − MPN entities.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few approaches have been performed to gain a deeper insight into aberrant miRNA regulation in leukaemia of myeloid origin [4][5][6][7], e.g. Philadelphia chromosomenegative chronic myeloproliferative neoplasm (Ph − MPN, including polycythaemia vera, PV, primary myelofibrosis, PMF, and essential thrombocythaemia, ET) [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Philadelphia chromosomenegative chronic myeloproliferative neoplasm (Ph − MPN, including polycythaemia vera, PV, primary myelofibrosis, PMF, and essential thrombocythaemia, ET) [4][5][6]. Characteristically 50-95% of Ph − MPN cases are positive for the Janus kinase 2 G1849T/V617F point mutation (JAK2 V617F ) [8] and ∼5% of PMF and ET cases show a G1544A/T/ W515K/L point mutation of the thrombopoietin receptor/ myeloproliferative leukaemia virus oncogene (MPL W515K/L ) [9] and one of the most prominent morphological features is an aberrant megakaryopoiesis [10].…”

Section: Introductionmentioning

confidence: 99%

“…down-regulation of miRNA 339 [5] and upregulation of miRNA 26b [6] in platelets, but no Ph − MPNderived bone marrow cells, particularly megakaryocytes in their natural intertrabecular environment, have been analysed [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

et al. 2008

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International audienceMicro RNA (miRNA) are small non-coding RNA molecules which have a post-transcriptional inhibitory regulation function, e.g. in megakaryopoiesis. A characteristic of Philadelphia chromosome-negative myeloproliferative neoplasm (Ph MPN) is the abundance of morphologically aberrant megakaryocytes. Based on previously published in vitro megakaryocytic differentiation assay data, we selected miRNA 10a, 17-5p, 20a and 126 and potential target proteins (HOXA1, RUNX1) for analysis of laser-microdissected bone marrow megakaryocytes from Ph MPN and controls ( = 66). Furthermore, we tested a potential influence of cytoreductive treatment on miRNA expression in bone marrow cells during the course of Ph MPN ( = 18). In summary, miRNA 17-5p, 20a and 126 are constitutively expressed in Ph MPN megakaryopoiesis while low or absent miRNA 10a appeared to correlate with strong megakaryocytic HOXA1 protein expression. No association to thrombocytosis, JAK2 mutations or cytoreductive treatment (bone marrow cells) were observed

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Role of TGF‐β1/miR‐382‐5p/SOD2 axis in the induction of oxidative stress in CD34+ cells from primary myelofibrosis

et al. 2018

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Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by an excessive production of pro‐inflammatory cytokines resulting in chronic inflammation and genomic instability. Besides the driver mutations in JAK2,MPL, and CALR genes, the deregulation of miRNA expression may also contribute to the pathogenesis of PMF. To this end, we recently reported the upregulation of miR‐382‐5p in PMF CD34+ cells. In order to unveil the mechanistic details of the role of miR‐382‐5p in pathogenesis of PMF, we performed gene expression profiling of CD34+ cells overexpressing miR‐382‐5p. Among the downregulated genes, we identified superoxide dismutase 2 (SOD2), which is a predicted target of miR‐382‐5p. Subsequently, we confirmed miR‐382‐5p/SOD2 interaction by luciferase assay and we showed that miR‐382‐5p overexpression in CD34+ cells causes the decrease in SOD2 activity leading to reactive oxygen species (ROS) accumulation and oxidative DNA damage. In addition, our data indicate that inhibition of miR‐382‐5p in PMF CD34+ cells restores SOD2 function, induces ROS disposal, and reduces DNA oxidation. Since the pro‐inflammatory cytokine transforming growth factor‐β1 (TGF‐β1) is a key player in PMF pathogenesis, we further investigated the effect of TGF‐β1 on ROS and miR‐382‐5p levels. Our data showed that TGF‐β1 treatment enhances miR‐382‐5p expression and reduces SOD2 activity leading to ROS accumulation. Finally, inhibition of TGF‐β1 signaling in PMF CD34+ cells by galunisertib significantly reduced miR‐382‐5p expression and ROS accumulation and restored SOD2 activity. As a whole, this study reports that TGF‐β1/miR‐382‐5p/SOD2 axis deregulation in PMF cells is linked to ROS overproduction that may contribute to enhanced oxidative stress and inflammation. Our results suggest that galunisertib may represent an effective drug reducing abnormal oxidative stress induced by TGF‐β1 in PMF patients.Database linkingGEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103464.

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MicroRNA expression profile in granulocytes from primary myelofibrosis patients

Cited by 71 publications

References 60 publications

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

Role of TGF‐β1/miR‐382‐5p/SOD2 axis in the induction of oxidative stress in CD34+ cells from primary myelofibrosis

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