Role of <i>miR-15a/miR-16-1</i> and the <i>TP53</i> axis in regulating telomerase expression in chronic lymphocytic leukemia

Rampazzo, Enrica; Bojnik, Engin; Trentin, Livio; Bonaldi, Laura; Bianco, Paola Del; Frezzato, Federica; Visentin, Andrea; Facco, Monica; Semenzato, Gianpietro; Rossi, Anita De

doi:10.3324/haematol.2016.157669

Cited by 13 publications

(11 citation statements)

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“…The expression of TERT is usually absent in non-neoplastic tissues but inappropriately activated in most tumours; its detection can thus be considered a specific marker of an ongoing neoplastic process ( Hanahan and Weinberg, 2011 ). A large number of studies, including our own ( Terrin et al , 2007 , Rampazzo et al , 2012 ; Bertorelle et al , 2013 ; Boscolo-Rizzo et al , 2015 ; Rampazzo et al , 2017 ), demonstrated that TERT is a prognostic marker of disease outcome for many types of lymphoid and solid malignancies ( Giunco et al , 2015 ). In addition, it has been demonstrated that circulating TERT levels can be detected in the plasma of colorectal cancer patients ( Lledó et al , 2004 , Terrin et al 2008 ) and are significantly correlated with those in tumour specimens ( Terrin et al , 2008 ), thus suggesting that plasma TERT may be a useful non-invasive marker for detecting and monitoring the disease.…”

Section: Discussionmentioning

confidence: 98%

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

et al. 2018

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Background:Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome.Methods:176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4–8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR.Results:Plasma levels of TERT were significantly lower at T2 (P<0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73–0.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10–4.11)-fold and 4.55 (95% CI 1.48–13.95)-fold higher, respectively, than those with undetectable plasma TERT levels.Conclusions:Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy.

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Section: Discussionmentioning

confidence: 98%

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

et al. 2018

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“…Patients with TP53 mutations are characterised by short telomers and high hTERT expression, a condition known to cause chromosome instability. 30,31 Patients with TP53 disrupted showed telomere deletion and chromosomal end-to-end fusion in cells with CK. 30 Thomay et al 32 reported that loss or mutation of TP53 caused an increased number of chromosomal break events leading to dicentric chromosome and whole-arm translocation.…”

Section: Discussionmentioning

confidence: 99%

The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia

et al. 2019

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BACKGROUND: Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1). METHODS: We performed a multicentre retrospective study to test whether the combination of CK subtypes with IGHV status could be a relevant prognostic and predictive tool. RESULTS: Among 522 patients 13% harboured CK2, 41% CK1 and/or U-IGHV (U-CK1) and 46% M-IGHV without any CK subtypes (M-noCK). After a median follow-up of 5.8 years, CK2 patients had the shortest TTFT (5-year TTFT 31%, 39 and 81%, p < 0.0001) and OS (5-year OS 67%, 85 and 93%, p < 0.0001) as compared to U-CK1 or M-noCK cases, regardless of TP53 abnormalities. CK2 patients also had the worst outcome after chemoimmunotherapy. In fact, the median TTNT after FCR or BR was 1.86 and 4.79 years for CK2 and U-CK1, but not reached for M-noCK patients (p < 0.0005). CONCLUSIONS: We herein suggest that the combined assessment of the IGHV mutational status and CK subtypes refines the prognostication of CLL, allowing to identify M-IGHV patients without any CK subtypes who are characterised by an indolent disease and excellent outcome after chemoimmunotherapy.

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“…They can act as oncogenic molecules or as tumor suppressors with a remarkable involvement in several B-CLL signaling pathways. They appear as crucial regulators of cellular procedures such as early B-cell development [ 45 ], cell metabolism and autophagy [ 46 , 47 ], of signaling pathways including the NFkB pathway [ 20 , 48 ], the Hedgehog (Hh) signaling pathway [ 49 ], as well as of key molecules in B-CLL such as BTK [ 50 ], TCL1A [ 51 , 52 , 53 ], BCL2 [ 54 ], TERT [ 55 ], and the heat shock proteins (HSPs) [ 56 ]. Moreover, they have an exceptional involvement in distinct parts of the BCR signaling pathway, which is abnormally activated in B-CLL, as well as, in its downstream pathways [ 57 ].…”

Section: Mirnas: Regulators Biomarkers and Potential Therapeutic mentioning

confidence: 99%

MicroRNAs: Tiny Regulators of Gene Expression with Pivotal Roles in Normal B-Cell Development and B-Cell Chronic Lymphocytic Leukemia

Katsaraki

Karousi

Artemaki

et al. 2021

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MicroRNAs (miRNAs) represent a class of small non-coding RNAs bearing regulatory potency. The implication of miRNAs in physiological cellular processes has been well documented so far. A typical process orchestrated by miRNAs is the normal B-cell development. A stage-specific expression pattern of miRNAs has been reported in the developmental procedure, as well as interactions with transcription factors that dictate B-cell development. Besides their involvement in normal hematopoiesis, miRNAs are severally implicated in hematological malignancies, a typical paradigm of which is B-cell chronic lymphocytic leukemia (B-CLL). B-CLL is a highly heterogeneous disease characterized by the accumulation of abnormal B cells in blood, bone marrow, lymph nodes, and spleen. Therefore, timely, specific, and sensitive assessment of the malignancy is vital. Several studies have attempted to highlight the remarkable significance of miRNAs as regulators of gene expression, biomarkers for diagnosis, prognosis, progression, and therapy response prediction, as well as molecules with potential therapeutic utility. This review seeks to outline the linkage between miRNA function in normal and malignant hematopoiesis by demonstrating the main benchmarks of the implication of miRNAs in the regulation of normal B-cell development, and to summarize the key findings about their value as regulators, biomarkers, or therapeutic targets in B-CLL.

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Role of miR-15a/miR-16-1 and the TP53 axis in regulating telomerase expression in chronic lymphocytic leukemia

Cited by 13 publications

References 15 publications

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia

MicroRNAs: Tiny Regulators of Gene Expression with Pivotal Roles in Normal B-Cell Development and B-Cell Chronic Lymphocytic Leukemia

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