Author:

Keywords:

Adult, Aged, Aged, 80 and over, Cell Line, Tumor, Enzyme Activation, Female, Genotype, Granulocytes, Heterozygote, Homozygote, Humans, Male, Middle Aged, Mitosis, Models, Molecular, Mouth Mucosa, Mutation, Missense, Myelofibrosis, Myeloid Metaplasia, Phosphorylation, Polycythemia Vera, Protein-Tyrosine Kinase, Proto-Oncogene Proteins, Recombination, Genetic, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Thrombocythemia, Hemorrhagic, Transfection, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, MYELOMONOCYTIC LEUKEMIA, FAMILIAL POLYCYTHEMIA, RET PROTOONCOGENE, IMATINIB MESYLATE, LUNG-CANCER, CELL-LINE, STEM-CELL, BCR-ABL, RECEPTOR, GENE, Janus Kinase 2, Primary Myelofibrosis, Protein-Tyrosine Kinases, Thrombocythemia, Essential, 1109 Neurosciences, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3101 Biochemistry and cell biology, 3211 Oncology and carcinogenesis

Abstract:

Polycythemia 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.