title: Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations.
abstract: We studied the lineage distribution of JAK2 mutations in peripheral blood of 8 polycythemia vera (PV) patients with exon 12 mutations and in 21 PV patients with JAK2-V617F. Using a quantitative allele discrimination assay, we detected exon 12 mutations in purified granulocytes, monocytes, and platelets of 8 patients studied, but lymphoid cells showed variable involvement and the mutation was absent in T cells. Endogenous erythroid colonies grew in all patients analyzed. One patient displayed erythroid colonies homozygous for the exon 12 mutation with evidence for mitotic recombination on chromosome 9p. In some patients with exon 12 mutations or JAK2-V617F, a proportion of endogenous erythroid colonies were negative for both JAK2 mutations. One patient carried 2 independent clones: one with an exon 12 mutation and a second with JAK2-V617F. The finding of clonal heterogeneity is compatible with the hypothesis that additional clonal events are involved in the pathogenesis of PV.
authors.affiliation: Department of Research, Experimental Hematology, University Hospital Basel, Switzerland.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.forename: Alexandre
authors.initials: A
authors.lastname: Theocharides
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000473:pathology; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D011087:Polycythemia Vera / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2