Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
| Autor: | Stefan Fröhling, Ayalew Tefferi, Peter Vandenberghe, Michael J. Eck, Jan Cools, Titus J. Boggon, Gerlinde Wernig, Ross L. Levine, Alan D. D'Andrea, Jeffrey C. Lee, James D. Griffin, Stacey Gabriel, Jennifer Adelsperger, Sumin Koo, Todd R. Golub, Peter Marynen, Thomas Mercher, D. Gary Gilliland, Iwona Wlodarska, Brian J. P. Huntly, William R. Sellers, Ruben A. Mesa, Sandra A. Moore, Stephanie J. Lee, Matthew Meyerson, Martha Wadleigh, Konstanze Döhner, Benjamin L. Ebert, Jennifer J. Clark |
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| Jazyk: | angličtina |
| Předmět: |
Adult
Male Models Molecular Heterozygote Cancer Research Ruxolitinib Genotype JAK2 Gene Mutation Mutation Missense Mitosis Biology Transfection chemistry.chemical_compound Polycythemia vera Cell Line Tumor Proto-Oncogene Proteins hemic and lymphatic diseases medicine Humans Phosphorylation Myelofibrosis Polycythemia Vera Myeloproliferative neoplasm Aged Aged 80 and over Recombination Genetic Janus kinase 2 Essential thrombocythemia Homozygote Mouth Mucosa Cell Biology Janus Kinase 2 Middle Aged Protein-Tyrosine Kinases TG101348 medicine.disease Enzyme Activation Oncology chemistry Primary Myelofibrosis Immunology Cancer research biology.protein Female Granulocytes Thrombocythemia Essential medicine.drug |
| Zdroj: | Cancer Cell. (4):387-397 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2005.03.023 |
| Popis: | SummaryPolycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase. |
| Databáze: | OpenAIRE |
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