Figure 1.
Inclusion criteria for various steps of analyses and IFNα dose. (A) Strategy of analysis and inclusion. Experimental observations were analyzed from progenitor and mature cells of the 48 patients of the cohort. We then excluded patients who had <2 data points (in progenitors and after the start of the therapy) for mathematical model calibration because there is no rationale to try to fit only 2 data points. To rigorously statistically analyze how IFNα doses differently impact molecular response according to the mutation type and zygosity in HSCs, we still had to exclude patients with no more than 5 progenitor type measurements from the start of the therapy for JAK2V617F patients. No CALRm patient was excluded because the model was less complex. The number in parentheses corresponds to the percentage of data used for the analyses. (B) To study the effect of IFNα on HSCs depending on the zygosity, it was necessary to exclude JAK2V617F patients whose clones exhibited too low CF over time. This analysis was not performed for CALRm MPN because only 2 of 12 patients had homozygous mutated cells. For our statistical analyses, a JAK2V617F patient was labeled as carrying homozygous (respectively heterozygous) subclones when CF >7% of homozygous (respectively heterozygous) progenitors were identified from ≥1 of the collected samples. Following this definition, some patients (8) could be considered carrying both heterozygous and homozygous subclones. Using this criterium, 17 patients carry heterozygous subclones and 10 patients carry homozygous subclones. (C) Averaged IFNα dose received over time by the 48 patients. Gray lines, individual dose; blue line, mean dose received by the 48 patients; shaded areas surrounding the curve, standard error of the mean.