hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia

Huh, Hee Jin; Yoo, Eun Sun; Seong, Chu-Myong; Lee, Mi-Ae; Hong, Kiseok; Chung, Wha Soon

doi:10.1002/ajh.20394

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…In this study, the highest value of hTERT mRNA was obtained in pre-B cell ALL and no correlation was also found between the blast percentages and the hTERT mRNA values. Similar results have been reported by Huh et al in AML patients and they suggested that hTERT value may be associated with the telomerase activity of blasts, not with the blast counts [6]. Our results may support this suggestion.…”

Section: Discussionsupporting

confidence: 91%

“…No significant difference was also found between the subgroups of those parameters except hemoglobin level. In the literature, there are a number of studies which found both significant and not significant correlation between the WBC count and TA [6,8,17,21]. In this study, the highest value of hTERT mRNA was obtained in pre-B cell ALL and no correlation was also found between the blast percentages and the hTERT mRNA values.…”

Section: Discussioncontrasting

confidence: 47%

“…It has been reported that telomerase activity (TA) shows biphasic pattern with aging and its level varies with the type of cancer cell [2][3][4][5]. The relation between hTERT mRNA and the known prognostic factors, risk groups, blast counts, cytogenetic abnormalities in leukemia patients have been evaluated in a limited number of studies, particularly in adult patients [6][7][8]. The diagnostic and prognostic importance of TA has also been studied in different hematological malignancies [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases

et al. 2008

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The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reverse-transcriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

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The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases

et al. 2008

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“…They hold the promise of being effective agents for the treatment of solid tumors [9,23,24]. A few investigations showed that the existence of hypoxic areas in tumor tissues and the expression of telomerase in cancer cells can be employed to achieve cancer targeting treatment [25][26][27][28][29][30][31]. Accordingly, the modifications to regulate SG600 with two promoters could restrict adenoviral replication to tumors and thus achieve better tumor-selective oncolysis.…”

Section: Discussionmentioning

confidence: 97%

A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines

et al. 2009

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PDCD5 (programmed cell death 5) accelerates apoptosis of certain tumor cells and the replication-defective Ad-PDCD5 may be a promising agent for enhancing chemosensitivity. In this study, a triple-regulated conditionally replicating adenoviruses (CRAd) carrying PDCD5 gene expression cassette, SG611-PDCD5, was engineered. In SG611-PDCD5, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the PDCD5 gene is controlled by the cytomegalovirus promoter. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several leukemic cell lines in vitro and in xenograft models of human leukemic cell line in nude mice. It was found by RQ-RT-PCR assay that SG611-PDCD5 expressed PDCD5 efficiently in leukemic cells. In K562 tumor xenograft models, SG611-PDCD5 displayed a tumor killing capacity. At a dose of 1 x 10(9) plaque-forming units, SG611-PDCD5 alone could completely inhibit the tumor growth and more effective than replication-defective Ad-PDCD5. Histopathologic examination revealed that SG611-PDCD5 administration resulted in leukemic cell apoptosis. We concluded that the triple-regulated SG611-PDCD5, as a more potent and safer antitumor therapeutic, could provide a new strategy for leukemia biotherapy.

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“…4,5 Telomerase activity and hTERT expression level in AML has been investigated in different works. [6][7][8] Recently, Huh et al 9 demonstrated by real-time RT-PCR that hTERT expression was higher in patients with AML at diagnosis and during relapse than during remission and that patients who failed to achieve complete remission had a high level of hTERT mRNA, this suggesting that hTERT mRNA may be a useful marker for prognosis prediction and disease monitoring in AML patients. Pharmacological telomere inhibition can sensitise drug-resistant and drug-sensitive cells to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Briatore¹,

Barrera²,

Pizzimenti³

et al. 2009

Cancer Biology & Therapy

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Telomerase enzyme, containing a catalytic subunit, the human telomerase reverse transcriptase (hTERT), and a small integral RNA component, synthesises the telomeres, the ends of eukaryotic chromosomes. Inhibition of telomerase activity leads the cells to senescence and death. Myelodysplastic syndromes (MSD) are hematological malignancies characterized by peripheral blood cytopenia and ineffective hematopoiesis. Telomerase activity and hTERT expression in MDS patients were independently investigated by different groups obtaining contradictory results. We analyzed telomerase activity and hTERT expression in the bone marrow of ten control, 15 MDS patients and two patients with AML, likely evolved from a previous MDS. Moreover, the expression of c-myc, mad1, p53 (transcription factors involved in hTERT expression regulation), has been investigated. Telomerase activity and hTERT expression increased in the MDS patients with respect to the controls. The analysis of the MDS subgroups, indicated that patients with more severe disease demonstrated significantly higher levels of hTERT expression and telomerase activity with respect to the patients with more favorable disease. c-Myc and p53 expressions were not significantly different between controls and MDS patients, whereas mad1 expression was increased in MDS patiens, particularly in those with more favorable disease. We hypothesize that mad1 increase can contribute to reduce the hTERT expression in the early stage of disease and we suggest that hTERT expression and telomerase activity, whether confirmed in larger series of cases could support other parameters in the diagnosis and stadiation of MDS.

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hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia

Cited by 14 publications

References 18 publications

The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases

The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases

A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines

Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

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