Figure 5.
HSC are targeted differently according to driver mutation type and zygosity and the IFNα doses. Molecular stem cell response factor (R factor) was predicted at the end of the survey (3000 days) for (i) heterozygous CALRm HSCs in patients treated with high vs low IFNα doses, (ii) heterozygous type 1 vs heterozygous type 2 CALRm HSCs, (iii) heterozygous vs homozygous JAK2V617F HSCs, (iv) heterozygous JAK2V617F HSCs in patients treated with high vs low IFNα doses, (v) homozygous JAK2V617F HSCs in patients treated with high vs low IFNα doses, and (vi) global JAK2V617F HSCs in patients treated with high vs low IFNα doses. The R factor is defined as the ratio (median value) between the inferred mutated HSC proportion after a given time of treatment (t = 3000 days) over the proportion of mutated HSCs at the initial time. Depending on the context, it refers to heterozygous or homozygous CF or VAF. Dash lines, R = 1 for no response, R > 1 for a negative response, and R < 1 for a positive response. R < 0.5 corresponds to a PMR, and R ∼ 0 corresponds to a complete molecular response. Solid lines, R median. R significantly differs between heterozygous CALRm HSC with low vs high IFNα doses (Mann-Whitney U test, P = .0087) and between type 1 CALRm and type 2 CALRm (Mann-Whitney U test, P = .0162). R significantly differs between heterozygous and homozygous JAK2V617F HSCs (Mann-Whitney U test, P = .0047). R tends to differ between heterozygous JAK2V617F HSCs treated with high vs low IFNα doses (Mann-Whitney U test, P = .0745). R significantly differs in the global JAK2V617F VAF in HSC between treatment with high and low doses of IFNα (Mann-Whitney U test, P = .0288). For each patient, we computed an average of received IFNα doses over the first 450 days of treatment. HD vs LD are defined according to the median dose of the groups of considered patients. The threshold is automatically computed to compare 2 subgroups of patients of the same size. The dose thresholds of IFNα are 78 µg/wk for heterozygous CALRm HSCs, 96.5 µg/wk for JAK2V617F HSCs, 96 µg/wk for heterozygous JAK2VF617F HSCs, and 108 µg/wk for homozygous JAK2V617F HSCs. Statistical differences were calculated using a Mann-Whitney U test: *P < .05, **P < .01.

HSC are targeted differently according to driver mutation type and zygosity and the IFNα doses. Molecular stem cell response factor (R factor) was predicted at the end of the survey (3000 days) for (i) heterozygous CALRm HSCs in patients treated with high vs low IFNα doses, (ii) heterozygous type 1 vs heterozygous type 2 CALRm HSCs, (iii) heterozygous vs homozygous JAK2V617F HSCs, (iv) heterozygous JAK2V617F HSCs in patients treated with high vs low IFNα doses, (v) homozygous JAK2V617F HSCs in patients treated with high vs low IFNα doses, and (vi) global JAK2V617F HSCs in patients treated with high vs low IFNα doses. The R factor is defined as the ratio (median value) between the inferred mutated HSC proportion after a given time of treatment (t = 3000 days) over the proportion of mutated HSCs at the initial time. Depending on the context, it refers to heterozygous or homozygous CF or VAF. Dash lines, R = 1 for no response, R > 1 for a negative response, and R < 1 for a positive response. R < 0.5 corresponds to a PMR, and R ∼ 0 corresponds to a complete molecular response. Solid lines, R median. R significantly differs between heterozygous CALRm HSC with low vs high IFNα doses (Mann-Whitney U test, P = .0087) and between type 1 CALRm and type 2 CALRm (Mann-Whitney U test, P = .0162). R significantly differs between heterozygous and homozygous JAK2V617F HSCs (Mann-Whitney U test, P = .0047). R tends to differ between heterozygous JAK2V617F HSCs treated with high vs low IFNα doses (Mann-Whitney U test, P = .0745). R significantly differs in the global JAK2V617F VAF in HSC between treatment with high and low doses of IFNα (Mann-Whitney U test, P = .0288). For each patient, we computed an average of received IFNα doses over the first 450 days of treatment. HD vs LD are defined according to the median dose of the groups of considered patients. The threshold is automatically computed to compare 2 subgroups of patients of the same size. The dose thresholds of IFNα are 78 µg/wk for heterozygous CALRm HSCs, 96.5 µg/wk for JAK2V617F HSCs, 96 µg/wk for heterozygous JAK2VF617F HSCs, and 108 µg/wk for homozygous JAK2V617F HSCs. Statistical differences were calculated using a Mann-Whitney U test: *P < .05, **P < .01.

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