Affiliation:
1. Department of Haematology, UCL Cancer Institute, London, United Kingdom
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.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
34 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献