title: Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients.
abstract: The modulation of JAK2 V617F allele burden dynamics was prospectively analysed in 47 patients (26 polycythaemia vera [PV] and 21 essential thrombocythaemia [ET]) treated with first-line hydroxyurea (HU) and compared with the JAK2 V617F dynamics of a control group of 45 PV and ET patients. A partial molecular response (PMR), according to European Leukaemia Net criteria, was observed in 27/47 (57%) patients. Median time to PMR was 14 months (3-66) with a probability of PMR at 3 years of 57%. A significant decrease in JAK2 V617F allele load was observed at 36 months both in PV and ET patients, being the reduction in PV higher than in ET patients (P = 0·01). A haematocrit ≥0·45 L/L was associated with a higher probability of attaining a PMR (HR:3·4; 95%CI:1·02-11·6, P = 0·04). Control group showed a slight increase of JAK2 V617F allele burden over time. The reduction in the mutated allele load comparing treated patients versus controls was highly significant both in PV and ET, demonstrating a clear effect of HU on the JAK2 V617F allele burden. In conclusion, first-line HU can attain PMR in more than 50% of newly diagnosed PV and ET patients, with a continuous decrease of the JAK2 V617F allele burden in PV patients during treatment.
authors.affiliation: Haematology Department Cancer Research Program Pathology Department, IMIM-Hospital del Mar Universitat Autònoma de Barcelona Methodological Consulting in Biomedical Research, Biomedical Research Park Universitat Pompeu Fabra, Barcelona, Spain. cbesses@parcdesalutmar.cat
authors.forename: Carlos
authors.initials: C
authors.lastname: Besses
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez-Larrán
authors.forename: Luz
authors.initials: L
authors.lastname: Martínez-Avilés
authors.forename: Sergi
authors.initials: S
authors.lastname: Mojal
authors.forename: Raquel
authors.initials: R
authors.lastname: Longarón
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.forename: Lourdes
authors.initials: L
authors.lastname: Florensa
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005500:Follow-Up Studies; D040741:Genetic Load; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics*; D011446:Prospective Studies; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea