Skip to main content
SpringerLink
Log in

Telomerase reverse transcriptase (TERT) A1062T mutation as a prognostic factor in Egyptian patients with acute myeloid leukemia (AML)

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

This study aimed to evaluate the incidence and clinical and prognostic impact of TERT A1062T mutation in AML patients treated at Mansoura Oncology Center. Screening for TERT A1062T mutation in exon 15 of the TERT gene was performed on diagnostic DNA samples from 153 AML patients and 197 healthy subjects as a control group by using sequence-specific primers. TERT A1062T mutation was detected in 18 cases out of 153 patients (11.8 %) and in one out of 197 control group subjects (0.51 %). The achievement of complete remission was significantly higher in AML group with wild type as compared to that in the mutant one (53.3 vs 16.7 %, respectively). In addition, the relapse rate was significantly higher in the mutant patients as compared to those with wild type (62.5 vs 28.2 %, respectively). The AML patients with TERT (A1062T) mutation had shorter overall survival than patients with wild type (P = 0.001). In a multivariable analysis, TERT (A1062T) mutational status is independently worse predictor factor (P = 0.007) when controlling for cytogenetic status (P = <0.001), performance status (P = <0.001) and bone marrow blast cells (P = 0.001). In conclusion, TERT A1062T mutation is an independent negative prognostic factor in AML patients. Therefore, molecular testing for TERT A1062T mutation in patients with AML is recommended in order to delineate their prognostic status.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Brown P. Adding WT1 to childhood AML alphabet soup. Blood. 2009;113(23):5696–7.

    Article  PubMed  CAS  Google Scholar 

  2. Gaidzik V, Schlenk R, Moschny S, Becker A, Bullinger L, Corbacioglu A, Krauter J, Brigitte S, Ganser A, Hartmut D, Konstanze D. Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML study group. Blood. 2009;113(19):4505–11.

    Article  PubMed  CAS  Google Scholar 

  3. Aalbers A, Calado R, Young N, Zwaan C, Wu C, Kajigaya S, Coenen E, Baruchel A, Geleijns K, de Haas V, Kaspers G, Kuijpers T, Reinhardt D, Trka J, Zimmermann M, Pieters R, van der Velden V, van den Heuvel-Eibrink M. Telomere length and telomerase complex mutations in pediatric acute myeloid leukemia. Leukemia. 2013;27(8):1786–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Tallman M. Relevance of pathologic classifications and diagnosis of acute myeloid leukemia to clinical trials and clinical practice. Cancer Treat Res. 2004;121:45–67.

    Article  PubMed  Google Scholar 

  5. Yamaguchi H, Calado R, Ly H, Kajigaya S, Baerlocher G, Chanock S, Lansdorp P, Young N. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005;352:1413–24.

    Article  PubMed  CAS  Google Scholar 

  6. Blackburn E. Switching and signaling at the telomere. Cell. 2001;106:661–73.

    Article  PubMed  CAS  Google Scholar 

  7. Lansdorp P. Telomeres, stem cells, and hematology. Blood. 2008;111:1759–66.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Vulliamy T, Marronel A, Szydlol R, Walnel A, Mason P, Dokal I. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet. 2004;36:447–9.

    Article  PubMed  CAS  Google Scholar 

  9. Calado R, Regal J, Hills M, Yewdell W, Dalmazzo L, Zago M, Lansdorp P, Hogge D, Chanock S, Estey E, Falcao R, Young N. Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc Natl Acad Sci USA. 2009;106(4):1187–92.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Kim H, Kojima K, Swindle C, Cotta C, Huo Y, Reddy V, Klug C. FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia. Blood. 2008;111:1567–74.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Rudolph K, Chang S, Lee H, Blasco M, Gottlieb G, Greider C, DePinho R. Longevity, stress response, and cancer in aging telomerase deficient mice. Cell. 1999;96:701–12.

    Article  PubMed  CAS  Google Scholar 

  12. Yan S, Han B, Li H, Wu Y, Zhou D, Zhao Y. Telomerase gene screening and telomere overhang detection in Chinese patients with myelodysplastic syndrome. Leuk Res. 2013;37(10):1359–62.

    Article  PubMed  CAS  Google Scholar 

  13. Wagner K, Anna Both A, Damm F,Thol F, Göhring G, Heuser M, Ottmann O, et al. Clinical impact of TERT A1062T mutations in younger patients with acute myeloblastic leukemia. In: 54th ASH Annual Meeting and Exposition 2012, Atlanta, GA.

  14. EL-Shakankiry N, EL-Sayed G, EL-Maghraby S, Moneer M. Bcl-2 protein expression in egyptian acute myeloid leukemia. J Egypt Nat Cancer Inst. 2009;21(1):71–6.

    PubMed  Google Scholar 

  15. de Lange T. Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol. 2005;70:197–204.

    Article  PubMed  Google Scholar 

  16. Artandi S, Rtandi S, Chang S, Lee S, Alson S, Gottlieb G, Chin L, DePinho R. Telomere dysfunction promotes nonreciprocal translocations and epithelial cancers in mice. Nature. 2000;406:641–5.

    Article  PubMed  CAS  Google Scholar 

  17. Gancarcíková M, Zemanová Z, Brezinová J, Berková A, Vcelíková S, Smigová J, Michalová K. The role of telomeres and telomerase complex in haematological neoplasia: the length of telomeres as a marker of carcinogenesis and prognosis of disease. Prague Med Rep. 2010;111(2):91–105.

    PubMed  Google Scholar 

  18. Ohyashiki K, Iwama H, Yahata N, Tauchi T, Kawakubo K, Shimamoto T, Ohyashiki J. Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation. Leuk Lymphoma. 2001;42(3):291–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura, Egypt

    Salah Aref & Mohamed Sabry El-Ghonemy

  2. Medical Hematology Unit, Mansoura Faculty of Medicine, Mansoura, Egypt

    Tarek Elsayed Abouzeid

  3. Medical Microbioloy and Immunology, Mansoura Faculty of Medicine, Mansoura, Egypt

    Amr Mohamed El-Sabbagh

  4. Medical Oncology Unit, Mansoura Oncology Center, Mansoura Faculty of Medicine, Mansoura, Egypt

    Mohamed Ali El-Baiomy

Authors
  1. Salah Aref
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohamed Sabry El-Ghonemy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tarek Elsayed Abouzeid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amr Mohamed El-Sabbagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed Ali El-Baiomy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salah Aref.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aref, S., El-Ghonemy, M.S., Abouzeid, T.E. et al. Telomerase reverse transcriptase (TERT) A1062T mutation as a prognostic factor in Egyptian patients with acute myeloid leukemia (AML). Med Oncol 31, 158 (2014). https://doi.org/10.1007/s12032-014-0158-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0158-6

Keywords

Search

Navigation