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Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders

Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders
Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders
The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.
0006-4971
2162-2168
Jones, Amy V.
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Kreil, Sebastian
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Zoi, Katerina
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Waghorn, Katherine
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Curtis, Claire
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Zhang, Lingyan
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Score, Joannah
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Seear, Rachel
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Chase, Andrew J.
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Grand, Francis H.
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White, Helen
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Zoi, Christine
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Loukopoulos, Dimitris
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Terpos, Evangelos
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Vervessou, Elisavet-Christine
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Schultheis, Beate
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Emig, Michael
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Ernst, Thomas
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Lengfelder, Eva
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Hehlmann, Rüdiger
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Hochhaus, Andreas
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Oscier, David
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Silver, Richard T.
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Reiter, Andreas
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Cross, Nicholas C.P.
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Jones, Amy V.
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Kreil, Sebastian
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Zoi, Katerina
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Waghorn, Katherine
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Curtis, Claire
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Zhang, Lingyan
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Score, Joannah
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Seear, Rachel
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Chase, Andrew J.
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Grand, Francis H.
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White, Helen
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Zoi, Christine
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Loukopoulos, Dimitris
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Terpos, Evangelos
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Vervessou, Elisavet-Christine
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Schultheis, Beate
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Emig, Michael
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Ernst, Thomas
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Lengfelder, Eva
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Hehlmann, Rüdiger
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Hochhaus, Andreas
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Oscier, David
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Silver, Richard T.
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Reiter, Andreas
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Cross, Nicholas C.P.
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Jones, Amy V., Kreil, Sebastian, Zoi, Katerina, Waghorn, Katherine, Curtis, Claire, Zhang, Lingyan, Score, Joannah, Seear, Rachel, Chase, Andrew J., Grand, Francis H., White, Helen, Zoi, Christine, Loukopoulos, Dimitris, Terpos, Evangelos, Vervessou, Elisavet-Christine, Schultheis, Beate, Emig, Michael, Ernst, Thomas, Lengfelder, Eva, Hehlmann, Rüdiger, Hochhaus, Andreas, Oscier, David, Silver, Richard T., Reiter, Andreas and Cross, Nicholas C.P. (2005) Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood, 106 (6), 2162-2168. (doi:10.1182/blood-2005-03-1320).

Record type: Article

Abstract

The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.

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Published date: 2005

Identifiers

Local EPrints ID: 24784
URI: http://eprints.soton.ac.uk/id/eprint/24784
ISSN: 0006-4971
PURE UUID: 771a70e6-aa43-447b-ba64-0d218767d575
ORCID for Andrew J. Chase: ORCID iD orcid.org/0000-0001-6617-9953
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 03 Apr 2006
Last modified: 16 Mar 2024 03:23

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Contributors

Author: Amy V. Jones
Author: Sebastian Kreil
Author: Katerina Zoi
Author: Katherine Waghorn
Author: Claire Curtis
Author: Lingyan Zhang
Author: Joannah Score
Author: Rachel Seear
Author: Andrew J. Chase ORCID iD
Author: Francis H. Grand
Author: Helen White
Author: Christine Zoi
Author: Dimitris Loukopoulos
Author: Evangelos Terpos
Author: Elisavet-Christine Vervessou
Author: Beate Schultheis
Author: Michael Emig
Author: Thomas Ernst
Author: Eva Lengfelder
Author: Rüdiger Hehlmann
Author: Andreas Hochhaus
Author: David Oscier
Author: Richard T. Silver
Author: Andreas Reiter

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