Hematopoietic progenitors are targeted differently according to the driver mutation type or zygosity and the IFNα dose. (A) Effect of IFNα in different hematopoietic compartments during the clinical survey of the 48 patients. Graph lines indicate the VAF calculated in CD34⁺ progenitors (i-ii) and measured in granulocytes (iii-iv) for CALR^m and MPL^m patients (i-iii) and JAK2^V617F patients (ii-iv). Thin lines, data from each patient harboring JAK2^V617F (dotted blue), CALR^m (dotted orange), or MPL^m (green); thick curves, smoothed averages (floating averages ±100 days) from the 32 JAK2^V617F (blue) or 14 CALR^m (orange) patient data; surrounding shaded areas, standard error of the mean. P values were calculated between CALR^m and JAK2^V617F data. Within the first 300 days, there was no significant difference between CALR^m and JAK2^V617F patient VAF. Significant differences between CALR^m and JAK2^V617F cases were observed starting from 600 days of treatment in the progenitor compartment using a Mann-Whitney U test (P < .0005). Less difference between CALR^m and JAK2^V617F VAF was observed in mature cells (P < .025 after 650 days). (B) Effect of IFNα according to driver mutation type or zygosity and the IFNα dose during the clinical survey. The VAF were computed by pooling the data from each of the 3 progenitor compartments for (i) patients with CALR^m MPN treated with IFNα at high doses (HD, >78 µg/wk on average) or low doses (LD, <78 µg/wk); (ii) patients with JAK2^V617F MPN treated with IFNα at HD (>96.5 µg/wk) or LD (<96.5 µg/wk); and (iii) JAK2^V617F heterozygous or homozygous progenitors independently of the doses. Thin line, data from a single patient; thick curves, smoothed averages (floating averages ±100 days) from the JAK2^V617F (blue) or CALR^m (orange) patient data; shaded areas surrounding the curve, standard error of the mean. Differences were calculated between heterozygous and homozygous JAK2^V617F progenitors after 600 days of treatment (Mann-Whitney U test, P < .03) and were significant after 1000 days of treatment (Mann-Whitney U test, P < .003).