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

Ayalew Tefferi, T. L. Lasho, J. Huang, C. Finke, R. A. Mesa, C. Y. Li, W. Wu, C. A. Hanson, Animesh D Pardanani

Research output: Contribution to journalArticle

175 Citations (Scopus)

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 × 109l-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.

Original languageEnglish (US)
Pages (from-to)756-761
Number of pages6
JournalLeukemia
Volume22
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Primary Myelofibrosis
Leukemia
Alleles
Survival
Platelet Count
Thrombosis
Clone Cells
Bone Marrow
Phenotype
Mutation
DNA
Incidence

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

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. / Tefferi, Ayalew; Lasho, T. L.; Huang, J.; Finke, C.; Mesa, R. A.; Li, C. Y.; Wu, W.; Hanson, C. A.; Pardanani, Animesh D.

In: Leukemia, Vol. 22, No. 4, 04.2008, p. 756-761.

Research output: Contribution to journalArticle

@article{f1b5413cda8544caa4a0c2a584a26cbd,
title = "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",
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 × 109l-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.",
author = "Ayalew Tefferi and Lasho, {T. L.} and J. Huang and C. Finke and Mesa, {R. A.} and Li, {C. Y.} and W. Wu and Hanson, {C. A.} and Pardanani, {Animesh D}",
year = "2008",
month = "4",
doi = "10.1038/sj.leu.2405097",
language = "English (US)",
volume = "22",
pages = "756--761",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - 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

AU - Tefferi, Ayalew

AU - Lasho, T. L.

AU - Huang, J.

AU - Finke, C.

AU - Mesa, R. A.

AU - Li, C. Y.

AU - Wu, W.

AU - Hanson, C. A.

AU - Pardanani, Animesh D

PY - 2008/4

Y1 - 2008/4

N2 - 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 × 109l-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.

AB - 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 × 109l-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.

UR - http://www.scopus.com/inward/record.url?scp=42449124578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449124578&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2405097

DO - 10.1038/sj.leu.2405097

M3 - Article

C2 - 18216871

AN - SCOPUS:42449124578

VL - 22

SP - 756

EP - 761

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 4

ER -