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Cited by 3,548Myeloproliferative Neoplasms: Diagnosis and TreatmentPlatelet Disorders and TreatmentsAcute Myeloid Leukemia Research

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Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders

Baxter, E Joanna, Scott, Linda M, Campbell, Peter J, East, Clare, Fourouclas, Nasios, Swanton, Soheila, Vassiliou, George S, Bench, Anthony J, Boyd, Elaine M, Curtin, Natasha, Scott, Mike A, Erber, Wendy N, Green, Anthony R·2005·The Lancet
DOI 10.1016/s0140-6736(05)71142-9
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Abstract

Background Human myeloproliferative disorders form a range of clonal haematological malignant diseases, the main members of which are polycythaemia vera, essential thrombocythaemia, and idiopathic myelofibrosis. The molecular pathogenesis of these disorders is unknown, but tyrosine kinases have been implicated in several related disorders. We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder. Methods We obtained DNA samples from patients with polycythaemia vera, essential thrombocythaemia, or idiopathic myelofibrosis. The coding exons of JAK2 were bidirectionally sequenced from peripheral-blood granulocytes, T cells, or both. Allele-specific PCR, molecular cytogenetic studies, microsatellite PCR, Affymetrix single nucleotide polymorphism array analyses, and colony assays were undertaken on subgroups of patients. Findings A single point mutation (Val617Phe) was identified in JAK2 in 71 (97%) of 73 patients with polycythaemia vera, 29 (57%) of 51 with essential thrombocythaemia, and eight (50%) of 16 with idiopathic myelofibrosis. The mutation is acquired, is present in a variable proportion of granulocytes, alters a highly conserved valine present in the negative regulatory JH2 domain, and is predicted to dysregulate kinase activity. It was heterozygous in most patients, homozygous in a subset as a result of mitotic recombination, and arose in a multipotent progenitor capable of giving rise to erythroid and myeloid cel…

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Metadata

Authors
Baxter, E. J., Scott, L. M., Campbell, P. J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G. S., Bench, A. J., Boyd, E. M., Curtin, N., Scott, M. A., Erber, W. N., & Green, A. R.
Affiliations
  • University of Cambridge (GB)
  • Addenbrooke's Hospital (GB)
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2005-03
Volume
365
Issue
9464
Pages
1054-1061
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(05)71142-9
OpenAlex
W2144664431
Cited by
3,548
References
0
Citations by year
2026: 66 · 2025: 77 · 2024: 98 · 2023: 126 · 2022: 130 · 2021: 141 · 2020: 145 · 2019: 135 · 2018: 126 · 2017: 158 · 2016: 176 · 2015: 204 · 2014: 193 · 2013: 201 · 2012: 210
FWCI
109.40
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust (088340)
Topics
  • Health Sciences › Medicine › Hematology › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
JAK2, myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, primary myelofibrosis, tyrosine kinase, acquired mutations, mitotic recombination, molecular pathogenesis
MeSH terms
Chromosomes, Human, Pair 9, Colony-Forming Units Assay, Granulocytes, Hematopoietic Stem Cells, Humans, Myeloproliferative Disorders, Polycythemia Vera, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Thrombocythemia, Essential, Signal Transduction, Polymerase Chain Reaction, Point Mutation, In Situ Hybridization, Fluorescence, Loss of Heterozygosity, Janus Kinase 2, Primary Myelofibrosis

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CoChat. (2026). Citation check: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. https://app.cochat.ai/papers/10.1016/s0140-6736(05)71142-9
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Baxter, E. J., Scott, L. M., Campbell, P. J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G. S., Bench, A. J., Boyd, E. M., Curtin, N., Scott, M. A., Erber, W. N., & Green, A. R. (2005). Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet. https://doi.org/10.1016/s0140-6736(05)71142-9