title: In essential thrombocythemia, multiple JAK2-V617F clones are present in most mutant-positive patients: a new disease paradigm.
abstract: In essential thrombocythemia (ET), the JAK2-V617F mutation is usually restricted to a subpopulation of neutrophils and platelets, and production of JAK2 wild-type (WT) platelets is not suppressed. Nonmutated precursor cells may, therefore, be susceptible to the acquisition of further JAK2 mutations. We used a common single nucleotide polymorphism (SNP) in the JAK2 coding sequence to genotype V617F alleles obtained either by allele-specific restriction enzyme digestion (RED) or by cloning. Both SNP alleles were detected in JAK2 mutant-positive alleles from neutrophils of 10 of 11 ET patients studied using RED compared with 0 of 5 with polycythemia vera. These results were confirmed in cloned products from 5 ET patients and indicate the occurrence of at least 2 separate JAK2 mutation events in the majority of ET patients investigated. In a further ET patient, JAK2 mutant-positive erythroid colonies with either X-allele inactivated were detected, demonstrating they could not have arisen from a common clonal precursor. These results indicate that at least 2 independent JAK2-V617F events occur commonly in ET patients, and they may arise on a polyclonal background. The presence of a JAK2 mutation in ET patients should not, therefore, be equated with a malignant disease.
authors.affiliation: Department of Haematology, UCL Cancer Institute, London, United Kingdom.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lambert
authors.forename: Tamara
authors.initials: T
authors.lastname: Everington
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Gale
mesh_terms: D000483:Alleles; D015672:Erythroid Precursor Cells / Q000473:pathology; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000473:pathology
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2