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

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.

journal_name

Leukemia

journal_title

Leukemia

authors

Bernard L,Belisle C,Mollica L,Provost S,Roy DC,Gilliland DG,Levine RL,Busque L

doi

10.1038/leu.2008.319

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

287-91

issue

2

eissn

0887-6924

issn

1476-5551

pii

leu2008319

journal_volume

23

pub_type

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