2009.10.01 – In essential thrombocythemia, multiple JAK2-V617F clones are present in most mutant-positive patients- a new disease paradigm
Blood, 1 October 2009, Vol. 114, No. 14, pp. 3018-3023.
In essential thrombocythemia, multiple JAK2-V617F clones are present in most mutant-positive patients: a new disease paradigm
Jonathan R. Lambert1, Tamara Everington1, David C. Linch1, and Rosemary E. Gale1
1 Department of Haematology, UCL Cancer Institute, London, United Kingdom
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.