title: X chromosome inactivation analysis reveals a difference in the biology of ET patients with JAK2 and CALR mutations.
abstract: Calreticulin mutations (CALR(MUT)) are found in a significant proportion of patients with essential thrombocythemia (ET) lacking JAK2(V617F) or MPL mutations. They are associated with substantially different hematological and clinical features and define a distinct subtype of ET. We show here that their presence is significantly correlated with a clonal X chromosome inactivation pattern (XCIP). Of 105 female ET patients investigated, 61 had an interpretable XCIP, and a clonal pattern was observed in 88% of CALR(MUT) patients compared with 26% of JAK2(V617F) (P = .0002) and 9% of JAK2(V617F)/MPL/CALR wild-type patients (P < .0001). Neutrophil CALR(MUT) level was significantly higher than JAK2(V617F) level (median, 50% vs 18%; P < .0001), and wild-type myelopoiesis was suppressed in CALR(MUT) but not JAK2(V617F) patients. These data are suggestive of truly monoclonal hematopoiesis in CALR(MUT) patients and provide further evidence that the biology associated with CALR mutations is markedly different from that of JAK2(V617F) mutations.
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Allen
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lambert
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Gale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D049951:X Chromosome Inactivation; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053614:Janus Kinase 2