Telomerase activity in acute myelogenous leukaemia: clinical and biological implications

Seol, Jae Goo; Kim, Eun Shil; Park, Woo Hyun; Jung, Chul Won; Kim, Byoung Kook; Lee, Young Yiul

doi:10.1046/j.1365-2141.1998.00524.x

Cited by 22 publications

(15 citation statements)

References 34 publications

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“…This is similar to findings obtained by the TRAP method (73-100%) [13,[17][18][19]. In our study, no significant difference of hTERT mRNA levels was noted between diagnosis and relapse (P > 0.05); in contrast, Xu et al observed that telomerase activity was significantly higher during relapse than at diagnosis [13].…”

Section: Discussionsupporting

confidence: 91%

“…In our study, hTERT mRNA expression was not associated with CD34 expression, white blood cell count, blast count, or chromosomal abnormalities (P > 0.05). Other studies have associated poor prognostic parameters with up-regulation of telomerase activity [13,19]. The level of telomerase activity of normal hematopoietic cells is determined by the stage of differentiation and proliferation [13].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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The purpose of this study was to investigate whether levels of hTERT mRNA, as determined by real-time RT-PCR, are associated with prognosis and clinical course in AML patients. Fifty-four bone marrow specimens from 21 patients diagnosed with de-novo AML were included. The level of hTERT mRNA was measured with the Telo TAGGG hTERT Quantification Kit (Roche Diagnostics, Mannheim, Germany), using a LightCycler Instrument (Roche Diagnostics). The level of hTERT mRNA was determined as the relative ratio (RR), which was calculated by dividing the level of hTERT mRNA by the level of the porphobilinogen deaminase (PBGD) housekeeping gene in the same samples [1,000 · (hTERT/PBGD)]. The expression rates of hTERT mRNA were significantly higher at diagnosis (73%) and during relapse (80%) than during remission (27%) (P < 0.05). The median RR for diagnosis or relapse was significantly higher than that for patients in remission (P < 0.05). hTERT mRNA expression was not correlated with CD34 expression, blast counts, white blood cell counts, or chromosomal abnormality (P > 0.05). Two patients who showed hTERT mRNA expression during remission (RR 3.14 and 7.15, respectively) relapsed after 1 month. Among seven patients with high hTERT mRNA levels (RR > 9.51), 4 failed to achieve complete remission (CR), whereas 4 of 5 patients without hTERT mRNA expression at diagnosis or during relapse achieved CR (P > 0.05). Patients showing a trend of increasing hTERT mRNA levels failed to reach a second CR after relapse, while those with a trend toward decreasing hTERT mRNA did achieve CR. Among eight samples showing hTERT mRNA expression in remission (RR > 0), 5 were obtained from patients who had received GCSF within 14 days. The expression rate and level of hTERT mRNA during remission were significantly higher in patients who had previously received GSCF (56%, RR = 0.15) than in other patients (15%, RR = 0) (P < 0.05). Serial and quantitative analysis of hTERT mRNA may be a useful marker for prediction of prognosis and monitoring in AML patients. Am.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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“…The enzyme telomerase, by maintaining telomeres at a certain minimum length, can extend the proliferative lifespan of cells [12]. High levels of telomerase activity (TA) are present in fetal hemopoietic stem cells [13], play a role in the immortalization of cells [14], and are characteristic of most malignancies [15]. Human telomerase comprises two major components: human telomerase RNA (hTR), which consists of 451 bases of integral RNA providing the template for the synthesis of the human telomeric repeat (TTAGGG)n [16], and human telomerase reverse transcriptase (hTERT), which is a 127-kDa protein providing catalytic function to replicate the ends of linear DNA [17].…”

Section: Introductionmentioning

confidence: 99%

Imbalance Between Apoptosis and Telomerase Activity in Myelodysplastic Syndromes: Possible Role in Ineffective Hemopoiesis

Ohshima¹,

Karube²,

Shimazaki³

et al. 2003

Leukemia & Lymphoma

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The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.

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“…N ormal human somatic cells progressively lose their telomeric sequence with repli cative senscence till cell "crisis" or apoptosis occurred [4,18,19] . I n contrast, almost all tumor cells and tissues express telomerase and maintain telomere length through an indefinite number of cell divisions [4][5][6][7][8][9][10][19][20][21][22][23][24] . Antisense hTR, hammerhead ribozyme TeloRZ and antisense oligonucleode agains t hTR could suppress tumor cell growth by inhibiting telomerase activity or shor tening TRF length [11][12][13] .…”

Section: Discussionmentioning

confidence: 99%

Antisense telomerase RNA induced human gastric cancer cell apoptosis

Zhang¹

2000

WJG

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Telomerase activity in acute myelogenous leukaemia: clinical and biological implications

Cited by 22 publications

References 34 publications

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

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

Imbalance Between Apoptosis and Telomerase Activity in Myelodysplastic Syndromes: Possible Role in Ineffective Hemopoiesis

Antisense telomerase RNA induced human gastric cancer cell apoptosis

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