Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia

Muhamed Baljevic, Bogdan Dumitriu, Ju Whei Lee, Elisabeth M. Paietta, Peter H. Wiernik, Janis Racevskis, Christina Chen, Eytan M. Stein, Robert E. Gallagher, Jacob M. Rowe, Frederick R. Appelbaum, Bayard L. Powell, Richard A. Larson, Steven E. Coutré, Jeffrey Lancet, Mark R. Litzow, Selina M. Luger, Neal S. Young, Martin S. Tallman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RARα-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL.

Original languageEnglish (US)
Pages (from-to)210-218
Number of pages9
JournalActa Haematologica
DOIs
StateAccepted/In press - Sep 16 2016

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Keywords

  • Acute promyelocytic leukemia
  • Disease risk factors
  • Telomere length

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology

Cite this

Baljevic, M., Dumitriu, B., Lee, J. W., Paietta, E. M., Wiernik, P. H., Racevskis, J., Chen, C., Stein, E. M., Gallagher, R. E., Rowe, J. M., Appelbaum, F. R., Powell, B. L., Larson, R. A., Coutré, S. E., Lancet, J., Litzow, M. R., Luger, S. M., Young, N. S., & Tallman, M. S. (Accepted/In press). Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia. Acta Haematologica, 210-218. https://doi.org/10.1159/000448160