Figure 5.
INCB053914 and ruxolitinib can synergize to inhibit the neoplastic growth of primary MPN cells. Primary peripheral blood mononuclear cells from JAK2V617F-positive MPN patients were plated in methylcellulose containing stem cell factor, interleukin-3, and GM-CSF, and colony formation was assessed in the presence of DMSO (0.1%), INCB053914, ruxolitinib, or the combination of the 2 drugs at the indicated concentrations. Epo-independent erythroid colony (EEC) formation (A) and CFU-G/M colony formation (B) were enumerated and are expressed as a percent of the number of colonies obtained with DMSO treatment. Sample 1 is from an essential thrombocythemia patient; samples 2, 3, 4, 6, 7, and 8 are from polycythemia vera patients; and sample 5 is from a patient with myelofibrosis. Additional information on the patients from which these samples were obtained is provided in supplemental Table 1. Samples 3 and 6 are from the same patient but samples were obtained about 6 months apart. Lower INCB053914 (5 nM) was assessed in the second sample (sample 6) because 20 nM was highly effective initially (sample 3). The sample remained sensitive to the combination even at this lower INCB053914 concentration. Error bars indicate SD. *P < .05; **P < .01. ns, not significant by unpaired Student t test. 

INCB053914 and ruxolitinib can synergize to inhibit the neoplastic growth of primary MPN cells. Primary peripheral blood mononuclear cells from JAK2V617F-positive MPN patients were plated in methylcellulose containing stem cell factor, interleukin-3, and GM-CSF, and colony formation was assessed in the presence of DMSO (0.1%), INCB053914, ruxolitinib, or the combination of the 2 drugs at the indicated concentrations. Epo-independent erythroid colony (EEC) formation (A) and CFU-G/M colony formation (B) were enumerated and are expressed as a percent of the number of colonies obtained with DMSO treatment. Sample 1 is from an essential thrombocythemia patient; samples 2, 3, 4, 6, 7, and 8 are from polycythemia vera patients; and sample 5 is from a patient with myelofibrosis. Additional information on the patients from which these samples were obtained is provided in supplemental Table 1. Samples 3 and 6 are from the same patient but samples were obtained about 6 months apart. Lower INCB053914 (5 nM) was assessed in the second sample (sample 6) because 20 nM was highly effective initially (sample 3). The sample remained sensitive to the combination even at this lower INCB053914 concentration. Error bars indicate SD. *P < .05; **P < .01. ns, not significant by unpaired Student t test. 

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