miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities

Mráz, Marek; Malinová, Karla; Kotašková, Jana; Pavlová, Šárka; Tichý, Boris; Malčíková, Jitka; Kozubík, Kateřina Staňo; Šmardová, Jana; Brychtová, Yvona; Doubek, Michael; Trbušek, Martin; Mayer, Jiřı́; Pospı́šilová, Šárka

doi:10.1038/leu.2008.377

Cited by 162 publications

(133 citation statements)

References 9 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: 79%

“…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.…”

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confidence: 77%

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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: 79%

supporting

confidence: 77%

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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“…[78][79][80] DPX-Survivac vaccine, which has been proved to be well tolerated and shows the clinical benefits in ovarian cancer in phase I clinical trial, 81 is currently being examined in diffuse large B-cell lymphoma patients with survivin expression in a phase II clinical trial. 82 Furthermore, incomplete Freund's adjuvant and type-I interferon (IFNα) are two adjuvants that can enhance survivin-specific antitumor immunity. 77,83,84 In summary, we identified survivin as an independent prognostic factor for poor outcome in activated B cell-like diffuse large B-cell lymphoma patients treated with R-CHOP.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

et al. 2015

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Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of 425%, associated with an International Prognostic Index score of 42 (P = 0.015), disease in ≥ 2 extranodal sites (P = 0.011), and a high Ki-67 index (Po 0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivinnegative patients (P = 0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P = 0.035 and P = 0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an

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“…This was associated with p53 mutations, chemotherapy (fludarabine)-refractory disease, impaired DNA damage response and decreased apoptosis. 64 Mraz et al 65 also found that miR-34a is consistently downregulated in CLL with p53 mutations. This implies that the detection of miR-34a expression may potentially be used as a predictor of therapy response.…”

Section: Mir-34 and Apoptosismentioning

confidence: 92%

The miR-34 family in cancer and apoptosis

2009

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miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities

Cited by 162 publications

References 9 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

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

The miR-34 family in cancer and apoptosis

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