microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification

Stamatopoulos, Basile; Meuleman, Nathalie; Haibe‐Kains, Benjamin; Saussoy, Pascale; Neste, Éric Van Den; Michaux, Lucienne; Heimann, Pierre; Martiat, Philippe; Bron, Dominique; Lagneaux, Laurence

doi:10.1182/blood-2008-11-189407

Cited by 224 publications

(153 citation statements)

References 35 publications

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Section: R E S E a R C H A R T I C L E M O L M Esupporting

confidence: 91%

“…In addition, we showed that this release was not specific to miR-150: indeed, when an irrelevant CLL microRNA was electroporated (as miR-1, which is normally absent in CLL), it was also released in a higher proportion from cellular miR-150 low patients (data not shown). This result is consistent with the fact that low levels of other microRNAs such as miR-34a, mir-29 and miR-223 have been observed in patients with poor prognostic CLL (21,33).Extracellular microRNA could circulate in body fluids in different forms: encapsulated in microvesicles, in exosomes or associated with protein/lipid complexes. In the present study, by using different speeds of centrifugation, we demonstrated that a small part of miR-150 circulates within microvesicles, but that the majority of circulating miR-150 is most likely associated with protein/lipid complexes because free microRNA will be rapidly degraded by RNAse.…”

supporting

confidence: 88%

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Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia

Stamatopoulos

Damme

Crompot

et al. 2015

Mol Med

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Recently, extracellular circulating microRNAs were also detected in body fluids, such as serum, plasma, saliva and urine (7). These circulating microRNAs are believed to be chaperoned by various carriers, such as secreted mem- MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL) physiopathology and prognosis. In addition, circulating microRNAs in body fluids have been proposed as new biomarkers. We investigated the expression of matched cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR) from purified CD19 + cells or from CLL serums obtained at diagnosis in a cohort of 273/252 CLL patients with a median follow-up of 78 months (range 7-380) and correlated it to other biological or clinical parameters. We showed that miR-150 was significantly overexpressed in CLL cells/serums compared with healthy subjects (P < 0.0001). Among CLL patients, a low cellular miR-150 expression level was associated with tumor burden, disease aggressiveness and poor prognostic factors. In contrast, a high level of serum miR-150 was associated with tumor burden markers and some markers of poor prognosis. Similarly, cellular and serum miR-150 also predicted treatment-free survival (TFS) and overall survival (OS) in an opposite manner: patients with low cellular/serum miR-150 levels have median TFS of 40/111 months compared with high-level patients who have a median TFS of 122/60 months (P < 0.0001/P = 0.0066). Similar results were observed for OS. We also found that cellular and serum miR-150 levels vary in an opposite manner during disease progression and that cellular miR-150 could be regulated by its release into the extracellular space. Cellular and serum levels of miR-150 are associated with opposite clinical prognoses and could be used to molecularly monitor disease evolution as a new prognostic factor in CLL. brane vesicles (exosomes from 50 to 100 nm and microvesicles from 100 nm to 1 μm) or protein/lipid complexes (8,9), since carrier-free microRNAs will be degraded by RNase digestion and other environmental factors (9). Their levels and composition have been shown to be modulated with injury conditions as well as tumor burden (10-12). For these reasons, extracellular microRNAs could be used as informative biomarkers to assess and monitor disease evolution (11,13). Moussay et al. (14) recently observed that some circulating microRNAs in CLL plasma could be used as prognostic factors. Among these, microRNA-150 warranted further investigation for a number of reasons. This microRNA plays an important role in normal and malignant hematopoiesis (15). In addition, plasma (14) and cellular (16,17) microRNA-150 were both downregulated in poor prognosis CLL patients based on ZAP70 and IgHV mutational status. A low level of cellular microRNA-150 was also observed in CLL proliferation centers (18), and microRNA-150 is differentially expressed according to the stereotyped B-cell receptor (BCR) subset taken into consideration (19), emphasizing its pivotal role in CLL. Finally, a recent s...

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Section: R E S E a R C H A R T I C L E M O L M Esupporting

confidence: 91%

supporting

confidence: 88%

Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia

Stamatopoulos

Damme

Crompot

et al. 2015

Mol Med

Self Cite

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“…The fact that neither miR-29 nor miR-181 is located at 11q chromosomal region suggests that deletions in this region may affect an unknown regulator of the expression of these two microRNAs 6 . These results were confirmed by Stamatopoulos et al who showed that miR-29c negative patients expressed significantly higher levels of Tcl-1 compared with miR-29c positive patients 62 .…”

Section: Mir-29 As a Regulator Of Tcl-1supporting

confidence: 80%

The role of miR-29 family members in malignant hematopoiesis

Kollinerová¹,

Vassanelli²,

Modrianský³

2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. MicroRNAs of the miR-29 family members were one of the first microRNAs identified as possible therapeutic agents in malignant hematopoiesis. The aim of our review is to summarize the current state of knowledge on miR-29 family members. Methods. We performed literature searches involving miR-29 family members and their relationship to individual hematological malignancies, namely acute myeloid leukemia (AML), chronic lymphoblastic leukemia (CLL) and chronic myeloid leukemia (CML). We also searched for subgroups of hematological malignancies, e.g. multiple myeloma, that are regarded as members of the acute or chronic types of leukemias. Results. A number of genes appear to be regulated by miR-29 family members in various physiological and pathological situations. In our view regulation of Tcl-1, Mcl-1 and DNA methyltransferases is relevant in case of hematological malignancies, hence these are the focus of this review. miR-29 family members also function during normal T-cell and B-cell development. Conclusion. MiR-29 family members appear to govern some general features in commonly heterogenous hematological malignancies and therefore form a potential target for treatment.

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“…Decrement of miR-223 is often observed in leukemia disease, 12 while increased expression of miR-223 is mainly seen in solid cancer types including HNSCC. 13,14 In the present study, we consistently found that miR-223 expression was enhanced in HNSCC cancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs as novel prognosis biomarkers for head and neck squamous cell carcinoma

Hou

Ishinaga²,

Midorikawa

et al. 2015

Cancer Biology & Therapy

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Keywords: biomarker, circulating miRNA, head and neck squamous cell carcinoma, miR-99a, miR-223Abbreviations: HNSCC, head and neck squamous cell carcinoma; miRNA, microRNA.Circulating microRNAs (miRNAs) are emerging as promising non-invasive biomarkers for human cancer. Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy worldwide, but its overall survival has remained unchanged in the past 3 decades. Biomarkers for evaluating efficacy of cancer therapy are urgently needed. To explore circulating miRNAs as cancer therapy biomarkers, we initially identified that 8 miRNAs were distinctly dysregulated in cancerous tissues compared with adjacent non-cancerous counterparts from 16 patients, using microarray and realtime PCR. Based on this discovery, the comparison study was performed between pre-and 6 months post-operative paired plasma samples on 9 patients. MiR-99a, which was down-regulated in cancerous tissues, was significantly increased in plasma after operation. Meanwhile, oncomiR miR-21 and miR-223 that were up-regulated in cancerous tissues, were significantly reduced in post-operative plasma samples. We firstly report the significant changes of miR99a in plasma of HNSCC patients after surgery. Furthermore, plasma miR-223 was inversely increased in a patient whose cancer relapsed within 6 months after operation. We conclude that these circulating miRNAs may serve as biomarkers to evaluate the efficacy of therapy and the prognosis of HNSCC.

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microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification

Cited by 224 publications

References 35 publications

Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia

Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia

The role of miR-29 family members in malignant hematopoiesis

Circulating microRNAs as novel prognosis biomarkers for head and neck squamous cell carcinoma

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