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Chronic Myeloproliferative Neoplasias

Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms

Leukemia volume 23, pages 287–291 (2009)Cite this article

Abstract

Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by chronic proliferation of hematopoietic progenitors. We studied the telomere length (TL) of 335 MPN patients and 93 gender- and age-matched controls using a quantitative PCR method (relative TL calculated as the ratio of the amount of telomere DNA vs single-copy DNA: T/S ratio). TL was markedly reduced in MPN patients compared with controls (T/S 0.561 vs 0.990, P<0.001). In JAK2V617F MPN patients, TL correlated inversely with allelic burden (P<0.001). Patients homozygous for the mutation (allelic burden 90–100%) had the shortest TL, even when compared with patients with lower allele burdens consistent with a dominant heterozygous population (allelic burden 55–65%) (T/S 0.367 vs 0.497, P=0.037). This suggests that the high degree of proliferation of the MPN clone reduces TL and suggests the possibility that TL shortening may be indicative of progressive genomic instability during MPN progression. The TL of JAK2V617F-negative MPN patients was similar to JAK2V617F-positive counterparts (T/S 0.527 vs 0.507, P=0.603), suggesting that the yet-to-be-discovered causative mutation(s) impact the mutated stem cell similarly to JAK2V617F, and that TL measurement may prove useful in the diagnostic workup of JAK2V617F-negative MPN.

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Acknowledgements

LM is an FRSQ scholar. DGG is an Investigator of the Howard Hughes Medical Institute, and a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award recipient. RLL is an American Society of Hematology Basic Research Fellow Award recipient, a Doris Duke Charitable Foundation Clinical Scientist Development Award recipient and is the Geoffrey Beene Junior Chair at Memorial Sloan Kettering Cancer Center.

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Author notes

  1. L Bernard and C Belisle: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Centre, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada

    L Bernard, C Belisle, L Mollica, S Provost, D-C Roy & L Busque

  2. Department of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada

    L Bernard, L Mollica, D-C Roy & L Busque

  3. Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

    L Bernard, L Mollica, D-C Roy & L Busque

  4. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA

    D G Gilliland & R L Levine

  5. Human Oncology and Pathogenesis Program, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    R L Levine

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  1. L Bernard
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Correspondence to L Busque.

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Bernard, L., Belisle, C., Mollica, L. et al. Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms. Leukemia 23, 287–291 (2009). https://doi.org/10.1038/leu.2008.319

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