Expression of the hTERT gene in patients with B-cell chronic lymphocytic leukemia

Česká verze

Authors: R. Plachý; J. Pavlíček; M. Jarošová; T. Papajík
Authors place of work: Hemato-onkologická klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Palackého v Olomouci
Published in the journal: Transfuze Hematol. dnes,15, 2009, No. 1, p. 10-12.
Category: Souhrnné práce, původní práce, kazuistiky

Summary

B-cell chronic lymphocytic leukemia (B-CLL) is clinically heterogeneous disease. Therefore it is very important to identify all reliable molecular and cellular markers to predict the tendency for disease progression. One of the promising prognostic markers seems to be expression of hTERT gene, which encodes catalytic subunit of human telomerase. We performed real-time reverse transcription PCR to quantitate the amount of hTERT transcripts in mononuclear blood cells from 47 B-CLL patients. We used ABL gene as a housekeeping gene.We compared the expression of hTERT to the IgV_H mutational status. Median of hTERT expression was fourfold higher in the IgV_H unmutated group than in the IgV_H mutated group (p<0.00001). The level of hTERT expression discriminated the IgV_H unmutated from IgV_H mutated B-CLL in 87% cases. Our results suggests that hTERT expression strongly correlates with IgV_H mutational status. Full understanding of the hTERT role in pathogenesis and progression of B-CLL could contribute to better prognostic stratification of patients with B-CLL.

Key words:
reverse telomerase, hTERT, B-CLL, mutational status of IgV_H

Zdroje

1. Huh HJ, Huh JW, Yoo ES et al. hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia. Am J Hematol 2005; 79 : 267–73.

2. Streutker CJ, Thorner P, Fabricius N et al. Telomerase activity as a prognostic factor in neuroblastomas. Pediatr Dev Pathol 2001; 4 : 62–7.

3. Terrin L, Trentin L, Degan M et al. Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same IgVH mutation status and different outcome. Leukemia 2007; 21 : 965–972.

4. van Dongen JJM, Langerak AW, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 2003; 17 : 2257–2317.

5. Thompsett AR, Ellison DW, Stevenson FK, et al. VH Gene Sequences From Primary Central Nervous System Lymphomas Indicate Derivation From Highly Mutated Germinal Center B Cells With Ongoing Mutational Activity. Blood 1999; 94 : 1738–1746.

6. Bechter OE, Eisterer W, Pall G. Telomere length and telomerase activity predict survival in patients with B-cell chronic lymphocytic leukemia. Cancer Res 1998; 58 : 4918–4922.

7. Damle RN, Batliwalla FM, Ghiotto F. Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by Ig V gene mutations. Blood 2004; 103 : 375–382.

8. Tchirkov A, Chaleteix C, Magnac C, et al. hTERT expression and prognosis in B-chronic lymphocytic leukemia. Ann Oncol., 2004; 15 : 1476–1480.

9. Hultdin M, Rosenquist R, Thunberg U, et al. Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications. Br J Cancer 2003; 88 : 593–598.

10. Cao Y, Li H, Deb S, et al. TERT regulates cell survival independent of telomerase enzymatic activity. Oncogene 2002; 21 : 3130–3138.

11. Deville L, Hillion J, Lanotte M, et al. Diagnostics, prognostic and therapeutic exploitation of telomeres and telomerase in leukemias. Curr Pharm Biotechnol 2006; 7 : 171–83.