TY - JOUR
T1 - Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients
AU - Besses, Carlos
AU - Álvarez-Larrán, Alberto
AU - Martínez-Avilés, Luz
AU - Mojal, Sergi
AU - Longarón, Raquel
AU - Salar, Antonio
AU - Florensa, Lourdes
AU - Serrano, Sergi
AU - Bellosillo, Beatriz
PY - 2011/2/1
Y1 - 2011/2/1
N2 - 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 14months (3-66) with a probability of PMR at 3years of 57%. A significant decrease in JAK2 V617F allele load was observed at 36months both in PV and ET patients, being the reduction in PV higher than in ET patients (P=0·01). A haematocrit ≥0·45L/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. © 2011 Blackwell Publishing Ltd.
AB - 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 14months (3-66) with a probability of PMR at 3years of 57%. A significant decrease in JAK2 V617F allele load was observed at 36months both in PV and ET patients, being the reduction in PV higher than in ET patients (P=0·01). A haematocrit ≥0·45L/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. © 2011 Blackwell Publishing Ltd.
KW - Allele burden
KW - Essential thrombocythaemia
KW - Hydroxyurea
KW - JAK2 V617F
KW - Polycythaemia vera
U2 - 10.1111/j.1365-2141.2010.08467.x
DO - 10.1111/j.1365-2141.2010.08467.x
M3 - Article
SN - 0007-1048
VL - 152
SP - 413
EP - 419
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -