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Chronic Myeloproliferative Disorders

Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival

Leukemia volume 22, pages 756–761 (2008)Cite this article

Abstract

The clinical relevance of JAK2V617F allele burden in primary myelofibrosis (PMF) has not been previously studied. Bone marrow-derived DNA from 199 patients with PMF was subjected to qualitative (n=199) and quantitative (n=129) analysis for V617F. Mutational frequency was 58% and median mutant allele burden ratio in V617F-positive patients was 29% (range, 1–74%). Multivariable analysis identified older age, platelet count ⩾100 × 109 l−1 and peripheral blood blast percentage <3% as being associated with a positive mutational status. The mere presence of the mutation did not affect the incidence of thrombosis (P=0.78), overall survival (P=0.22) or leukemia-free survival (P=0.5). The 129 patients with allele burden information were divided into four groups: V617F-negative (n=53) and V617F-positive with mutant allele burden in the lower quartile (n=19), middle quartiles (n=38) or upper quartile (n=19) range. Kaplan–Meier plots revealed significantly shortened overall (P=0.0008) and leukemia-free (P=0.01) survival for the lower quartile, but not for upper quartile allele burden group; independent prognostic relevance was validated by multivariable analysis. We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine,,

    A Tefferi, T L Lasho, J Huang, C Finke, R A Mesa & A Pardanani

  2. Mayo Clinic, Rochester, MN, USA

    A Tefferi, T L Lasho, J Huang, C Finke, R A Mesa & A Pardanani

  3. Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    C Y Li & C A Hanson

  4. Division of Health Sciences Research, Department of Biostatistics, Mayo Clinic, Rochester, MN, USA

    W Wu

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  1. A Tefferi
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  2. T L Lasho
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Correspondence to A Tefferi.

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Tefferi, A., Lasho, T., Huang, J. et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 22, 756–761 (2008). https://doi.org/10.1038/sj.leu.2405097

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