6533b856fe1ef96bd12b2720

RESEARCH PRODUCT

Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy

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Abstract Objective: To analyse the effect of hydroxyurea (HU) on the JAK2-V617F allelic ratio (%JAK2-V617F) of patients with Polycythaemia Vera (PV) and Essential Thrombocythaemia (ET). Methods: Thirty-six patients were examined sequentially prior to and after on-set of (HU) therapy (8 PV, 17 ET), or while remaining untreated (2 PV, 9 ET). For all patients, the %JAK2-V617F was determined in purified blood granulocytes using sensitive allele-specific, quantitative PCRs. In a second study, two distinct groups of patients were examined at a single time point at the time of diagnosis (99 PV, 178 ET) or while receiving HU (36 PV, 98 ET). Results: HU therapy (median duration: 15 months) reduced the %JAK2V617F by >30% in 13/25 patients (4 PV, 9 ET). For 3 patients, JAK2V617F remained undetectable for 3–27 months. There was no significant change in %JAK2-V617F for the 11 patients who received no treatment. In the single time point study of two large cohorts, the mean %JAK2-V617F was lower for patients with HU therapy (median duration: 32 months) than for patients at diagnosis (24% vs. 33%, p<0.01). However, when analysed by gender, the decrease in %JAK2-V617F was significant only in female patients; this was true for both PV (39% vs. 52%, p=0.0249) and ET (12% vs. 17%, p=0.0364). Conclusion: Reduction and even the disappearance of the JAK2-V617F-mutated clone can be obtained with HU therapy in PV and ET patients, most likely within the first two years of treatment.