Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms Academic Article uri icon

Overview

MeSH Major

  • Janus Kinase 2
  • Mutation, Missense
  • Myeloproliferative Disorders
  • Telomere

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.

publication date

  • January 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4640467

Digital Object Identifier (DOI)

  • 10.1038/leu.2008.319

PubMed ID

  • 19005480

Additional Document Info

start page

  • 287

end page

  • 91

volume

  • 23

number

  • 2