Hydroxyurea dose impacts hematologic parameters in polycythemia vera and essential thrombocythemia but does not appreciably affect JAK2-V617F allele burden.

A recent publication by Antonioli et al. shows that the continuous use of hydroxyurea (HU) does not appreciably reduce JAK2 V617F allele burden in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Our results confirm and extend these data. To assess the effects of a cytoreductive treatment on the JAK2-V617F allelic ratio, a single center retrospective study in myeloproliferative neoplasm (MPN) patients was performed. The effect of HU on the JAK2-V617F allele burden was evaluated in at least two sequential samples of 21 patients with PV or ET submitted to HU therapy and referred for molecular diagnosis. The JAK2V617F allele load was measured by an allele-specific PCR with fluorescent primers in DNA of density gradient purified granulocytes according to Jones et al. with slight modifications. As standards, serial dilutions of plasmids carrying the wild-type and V617F mutated JAK2 sequences were used. JAK2-V617F allele burden was determined based on availability of serial samples of genomic DNA, laboratory data and clinical records of the 8 PV and 13 ET (one of them transforming to acute leukemia) patients, as shown in Figure 1. The JAK2V617F allele burden was evaluated before and/or after initiation of HU therapy and compared to the last sample that was available during treatment. We herein correlate changes in the JAK2-V617F allele burden with HU dose variation; hematocrit (Ht) and platelet counts during HU treatment for PV (Figure 2A) and ET patients (Figure 2B). Hydroxyurea usage was consistently associated with hematologic changes over time (Table 1). However, while HU dosage importantly impacted Ht (PV patients 3, 7, and 63) and platelet count (ET patients 4, 6, 10, 11 and 31), JAK2-V617F allele burden did not necessarily vary according to changes in HU doses. Although 3 PV patients (1, 2, and 3) and 5 ET patients (18, 31, 34, 51 and 54) evolved with JAK2 fluctuations, these oscillations did not significantly impact allele burden over time. In general, the percentage of JAK2-V617F allele burden tended to remain stable through HU treatments. While fluctuations with reductions of JAK2-V617F allele burden were seen when comparing pre-treatment JAK2-V617F allele load with the latest sample, patients with longer follow ups evolved with a stable allelic burden despite variations in hematologic counts and HU