Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Briatore, Federica; Barrera, Giuseppina; Pizzimenti, Stefania; Toaldo, Cristina; Casa, Chiara Della; Laurora, Stefano; Pettazzoni, Piergiorgio; Dianzani, Mario U.; Ferrero, Dario

doi:10.4161/cbt.8.10.8130

Cited by 34 publications

(28 citation statements)

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“…In other words, Madl and c-Myc function as opposite competitive inhibitors [43][44][45]. Briatore et al [46]. showed that in patients with myelodysplastic syndromes, hTERT expression is related to transcription factors c-Myc, Mad1 and p53.…”

Section: And Sox2mentioning

confidence: 99%

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

Shen

Chen

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cancer stem cells (CSCs) are important factors for the continuous growth, recurrence, and metastasis of malignant tumors. They are responsible for the ineffectiveness of traditional radiotherapy and chemotherapy toward malignant tumors. Currently, stem cells or side-population cells have been isolated from many cancer cell lines and malignant tumor tissues, including nasopharyngeal carcinoma. Exploring the biological characteristics of CSCs for CSC-targeted therapy has gained importance. CSCs possess higher telomerase activity; thus, the use of the gene encoding telomerase inhibitor PinX1 gene to target telomerase in CSCs and inhibit proliferation, invasion, and metastasis of CSCs has become an important means for the treatment of malignant tumors. PinX1 may regulate complex pathways, including TRF1, Mad1/c-Myc, and p53. Methods: In this study, nasopharyngeal CD133+ CSCs were sorted using CD133 immunomagnetic beads by flow cytometry The successful isolation of CD133+ CSCs was confirmed by examining their surface markers, namely CD44, NaNOG, and SOX2 as well as their ability to undergo in vivo tumorigenesis and in vitro sphere formation, proliferation, migration, and invasion. In addition, CD133+ CSCs were transfected with the constructed PinX1 overexpression plasmid or siRNA and the resulting effects on their proliferation, migration, invasion, and apoptosis were detected using cell counting kit-8 (CCK-8), transwell assay, and scratch test, respectively. Furthermore, their effects on mRNA and protein levels of TRF1, TRF2, Mad1, c-Myc, and p53 were examined using quantitative real-time PCR and western blot, respectively. Results: The overexpression of PinX1 in CD133⁺ CSCs significantly decreased hTERT (P < 0.001), inhibited proliferation, migration, and invasion, induced apoptosis, and significantly decreased c-Myc mRNA levels (P < 0.001), while it increased TRF1, Mad1, and p53 mRNA levels (all P < 0.001). On the other hand, PinX1 silencing in CD133⁺ CSCs significantly decreased TRF1, Mad1, and p53 mRNA levels (all P < 0.01), while it increased hTERT and c-Myc mRNA levels (all P < 0.05). Conclusion: These results indicate that PinX1 downregulates telomerase activity in CD133⁺ CSCs, inhibits its proliferation, migration, and invasion, and induces apoptosis possibly through TRF1, Mad1/c-Myc, and p53–mediated pathways.

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Section: And Sox2mentioning

confidence: 99%

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

Shen

Chen

Wang

et al. 2018

Cell Physiol Biochem

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“…22 Several studies found a relationship between levels of hTERT expression, telomerase activity and clinical aggressiveness of a variety of malignancies, including leukemia and lymphoma. [23][24][25] It has also been demonstrated that telomerase activity, or hTERT expression, may be a prognostic indicator of overall survival in B-CLL. [26][27][28] To date, only one study has analyzed both telomeres and telomerase in the same B-CLL patients and showed that patients with unmutated IGVH had shorter telomeres and higher telomerase activity than mutated IGVH cases.…”

Section: Introductionmentioning

confidence: 99%

Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes

Rampazzo¹,

Bonaldi²,

Trentin³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundB-cell chronic lymphocytic leukemia is a clinically heterogeneous disease; some patients rapidly progress and die within a few years of diagnosis, whereas others have a long life expectancy with minimal or no treatment. Telomere length and telomerase levels have been proposed as prognostic factors; however, very few cases have been characterized for both parameters and no study has analyzed the prognostic value of the telomere/telomerase profile. Design and MethodsOne hundred and seventy-three cases of chronic lymphocytic leukemia were characterized for telomere lengths and telomerase levels by real-time polymerase chain reaction. Data were correlated with established prognostic markers, IGVH mutational status and chromosomal aberrations, and clinical outcome. ResultsTelomere lengths were inversely correlated with telomerase levels (rs= -0.213; P=0.012), and most of the cases of chronic lymphocytic leukemia with high levels (above median) of telomerase had short (below median) telomeres (P=0.0001). Telomerase levels were higher and telomeres were shorter in unmutated IGVH cases than in mutated IGVH ones (P<0.0001). Chronic lymphocytic leukemias with 11q, 17p deletion or 12 trisomy had significantly higher levels of telomerase and shorter telomeres than those with no chromosomal aberration or the sole 13q deletion (P<0.001). Telomere length/telomerase level profiles identified subgroups of patients with different clinical outcomes (P<0.0001), even within the subsets of chronic lymphocytic leukemia defined by IGVH mutational status or chromosomal aberrations. Short telomere/high telomerase profile was independently associated with more rapid disease progression. ConclusionsComprehensive analyses of telomeres, telomerase, chromosomal aberrations, and IGVH mutational status delineate groups of chronic lymphocytic leukemias with distinct biological characteristics and clinical outcomes. The telomere/telomerase profile may be particularly useful in refining the prognosis of chronic lymphocytic leukemia patients with mutated IGVH and no high-risk chromosomal aberrations.Key words: B-CLL, telomere, telomerase, chromosomal aberrations. Bonaldi L, Trentin L, Visco C, Keppel S, Giunco S, Frezzato F, Facco M, Novella E, Giaretta I, Del Bianco P, Semenzato G, and De Rossi A. Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes. Haematologica 2012;97(1):56-63. doi:10.3324/haematol.2011 Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes

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“…64,65 Telomerase activity and hTERT expression is increased in marrow cells from patients with MDS, and patients with more severe disease showed significantly higher levels of hTERT expression and telomerase activity than those with more favorable disease. 66 These data suggest the potential role of altered telomere dynamics in MDS progression.…”

Section: Altered Telomere Dynamicsmentioning

confidence: 82%

The Multifaceted Nature of Myelodysplastic Syndromes: Clinical, Molecular, and Biological Prognostic Features

Greenberg

2013

J Natl Compr Canc Netw

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The myelodysplastic syndromes (MDS) consist of a heterogeneous spectrum of myeloid clonal hemopathies. The Revised International Prognostic Scoring System (IPSS-R) provides a recently refined method for clinically evaluating the prognosis of patients with MDS. Molecular profiling has recently generated extensive data describing critical hematopoietic molecular and biologic derangements contributing to clinical phenotypes. Current molecular insights have demonstrated roles of specific somatic gene mutations in the development and clinical outcomes of MDS, including their propensity to progress to more aggressive stages, such as acute myeloid leukemia. This article focuses on these recently reported clinical and underlying pathogenetic findings. The discussion provides a synthesis of the prognostic clinical, molecular, and biologic abnormalities intrinsic to the aberrant marrow hematopoietic and microenvironmental influences in MDS. (JNCCN 2013;11:877-885) NCCN: Continuing Education Accreditation StatementThis activity has been designated to meet the educational needs of physicians and nurses involved in the management of patients with cancer. There is no fee for this article. No commercial support was received for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians.NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center`s Commission on Accreditation.This activity is accredited for 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 70% minimum passing score and complete the evaluation at http://education.nccn.org/ node/23880; and 4) view/print certificate.Release date: July 12, 2013; Expiration date: July 12, 2014 Learning ObjectivesUpon completion of this activity, participants will be able to:• Clinical Features Prognostic CharacterizationThe International Prognostic Scoring System (IPSS) has been an important standard for assessing the prognosis of adult patients with untreated primary MDS.1 However, since its publication in 1997, additional prognostic systems have been suggested providing other parameters to indicate meaningful differences in clinical outcomes, 2-5 and the WHO hematopathologists added a morphologic refinem...

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Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Cited by 34 publications

References 43 publications

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes

The Multifaceted Nature of Myelodysplastic Syndromes: Clinical, Molecular, and Biological Prognostic Features

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