title: X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis.
abstract: The JAK2V617F mutation is present in most patients with polycythemia vera (PV) and in some patients with essential thrombocythemia (ET) and myeloid metaplasia/myelofibrosis (MMM). We sought to investigate the relationship between granulocyte clonality and JAK2V617F allelic ratio. A total of 168 of 190 female patients were informative for a clonality assay at the HUMARA locus; 80% of MMM, 75% of PV, and 67% of ET patients demonstrated clonal granulopoiesis. The JAK2V617F allele was detected by quantitative real-time polymerase chain reaction (PCR) in 99% of PV, 72% of ET, and 39% of MMM. A correlation between clonality and JAK2V617F allelic ratio was demonstrated for PV (P < .001) but not for ET or MMM (both P > .6). These data suggest that acquisition of the JAK2V617F mutation may be sufficient for the development of PV, but additional genetic events are necessary in ET and MMM. In addition, some ET and MMM patients with clonal granulopoiesis have somatic mutations other than JAK2V617F.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Claude
authors.initials: C
authors.lastname: Belisle
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lee
authors.forename: Pierre
authors.initials: P
authors.lastname: Chagnon
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Lambert
authors.initials: L
authors.lastname: Busque
mesh_terms: D019943:Amino Acid Substitution; D041321:Chromosomes, Human, X; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D053614:Janus Kinase 2; D011087:Polycythemia Vera / Q000235:genetics*; D016133:Polymerase Chain Reaction; D055728:Primary Myelofibrosis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012729:Sex Chromosome Aberrations; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2