Combined administration of navitoclax is able to maintain the efficacy of pegIFNα in reducing MPN-associated hematological disease parameters, in addition to potentiating apoptosis in Jak2V617F HSPCs. (A) Experimental schematic for determining the effect of single doses of pegIFNα (600 ng) and navitoclax (100 mg/kg) in Jak2VF chimeric BM mice (B-H, n = 9-10/group). (B) The percentage of hematocrit (HCT) of the chimeric mice. (C) The percentage of reticulocytes in the peripheral blood of chimeric mice. (D) The spleen weight of the chimeric mice. (E) The percentage of R2 erythroblasts (CD71+/Ter119+) in the spleen of the chimeric mice. (F) Bar graph (left) and example flow cytometry data (right) demonstrating the percentage of cleaved caspase-3+ HSPCs (Lin–/Sca1+/Kit+) in the BM of the chimeric mice. (G) The percentage of cleaved caspase-3+ LT-HSCs in the BM of the chimeric mice. (H) The percentage of cleaved caspase-3+ WT and VF HSPCs in the BM of the chimeric mice. (I) Experimental schematic for determining the effect of single doses of pegIFNα (600 ng) and navitoclax (100 mg/kg) or venetoclax (100 mg/kg) in Jak2VF chimeric BM mice (J-L, n = 5-6/group). (J) Bar graph (left) and example flow cytometry data (right) demonstrating the percentage of cleaved caspase-3+ HSPCs in the BM of the chimeric mice. (K) The percentage of cleaved caspase-3+ WT and VF HSPCs in the BM of the chimeric mice. (L) The percentage of cleaved caspase 3+ LT-HSCs in the BM of the chimeric mice. (M) Platelet and neutrophil numbers in the peripheral blood of chimeric mice. Individual data points represent data generated from independent recipient mice. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Different symbols for data points on the same plot denote different cohorts. SP, spleen; WBM, whole bone marrow.

Combined administration of navitoclax is able to maintain the efficacy of pegIFNα in reducing MPN-associated hematological disease parameters, in addition to potentiating apoptosis in Jak2V617F HSPCs. (A) Experimental schematic for determining the effect of single doses of pegIFNα (600 ng) and navitoclax (100 mg/kg) in Jak2VF chimeric BM mice (B-H, n = 9-10/group). (B) The percentage of hematocrit (HCT) of the chimeric mice. (C) The percentage of reticulocytes in the peripheral blood of chimeric mice. (D) The spleen weight of the chimeric mice. (E) The percentage of R2 erythroblasts (CD71+/Ter119+) in the spleen of the chimeric mice. (F) Bar graph (left) and example flow cytometry data (right) demonstrating the percentage of cleaved caspase-3+ HSPCs (Lin–/Sca1+/Kit+) in the BM of the chimeric mice. (G) The percentage of cleaved caspase-3+ LT-HSCs in the BM of the chimeric mice. (H) The percentage of cleaved caspase-3+ WT and VF HSPCs in the BM of the chimeric mice. (I) Experimental schematic for determining the effect of single doses of pegIFNα (600 ng) and navitoclax (100 mg/kg) or venetoclax (100 mg/kg) in Jak2VF chimeric BM mice (J-L, n = 5-6/group). (J) Bar graph (left) and example flow cytometry data (right) demonstrating the percentage of cleaved caspase-3+ HSPCs in the BM of the chimeric mice. (K) The percentage of cleaved caspase-3+ WT and VF HSPCs in the BM of the chimeric mice. (L) The percentage of cleaved caspase 3+ LT-HSCs in the BM of the chimeric mice. (M) Platelet and neutrophil numbers in the peripheral blood of chimeric mice. Individual data points represent data generated from independent recipient mice. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Different symbols for data points on the same plot denote different cohorts. SP, spleen; WBM, whole bone marrow.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal