Figure 2.
Pluripotin abolishes the adaptive resistance conferred by RASmutants, BCR-ABL, and Jak2V617. Dose-response sigmoidal curve showing the proliferation of Ba/F3 cells expressing FLT3ITD and cooperating mutants BCR-ABL, RASG12V, and Jak2V617F implicated in adaptive resistance. A dose-dependent cell proliferation showing resistance to gilteritinib (A) although treatment with pluripotin fully inhibited their proliferation (B). (C) A comparative immunoblot analysis showing inhibition of FLT3, ERK1/2, and STAT5. Total cell extracts from the BaF3-FLT3ITD and BaF3-FLT3ITD/RASG12V cells treated with gilteritinib or pluripotin for 2 hours were probed with anti-pFLT3, anti-pSTAT5, anti-pERK1/2, anti-FLT3, anti-ERK1/2, and anti-STAT5 antibodies. The sigmoidal curves showing the proliferation of human AML cell lines, MOLM13 and MV4-11, expressing RasG12V and RASQ61K resistant to gilteritinib (D) whereas pluripotin treatment fully inhibited their proliferation (E). (F) Immunoblot analysis showing inhibition of proliferation is owing to on-target inhibition of FLT3, ERK1/2, and STAT5. Total cell extracts from the AML cells treated with pluripotin for 2 hours were probed with anti-pFLT3, anti-pSTAT5, anti-pERK1/2, anti-FLT3, anti-ERK1/2, and anti-STAT5 antibodies. Representative cell proliferation data and western blottings are shown from 2 independent experiments. Error bars represent ± SD.

Pluripotin abolishes the adaptive resistance conferred by RASmutants, BCR-ABL, and Jak2V617. Dose-response sigmoidal curve showing the proliferation of Ba/F3 cells expressing FLT3ITD and cooperating mutants BCR-ABL, RASG12V, and Jak2V617F implicated in adaptive resistance. A dose-dependent cell proliferation showing resistance to gilteritinib (A) although treatment with pluripotin fully inhibited their proliferation (B). (C) A comparative immunoblot analysis showing inhibition of FLT3, ERK1/2, and STAT5. Total cell extracts from the BaF3-FLT3ITD and BaF3-FLT3ITD/RASG12V cells treated with gilteritinib or pluripotin for 2 hours were probed with anti-pFLT3, anti-pSTAT5, anti-pERK1/2, anti-FLT3, anti-ERK1/2, and anti-STAT5 antibodies. The sigmoidal curves showing the proliferation of human AML cell lines, MOLM13 and MV4-11, expressing RasG12V and RASQ61K resistant to gilteritinib (D) whereas pluripotin treatment fully inhibited their proliferation (E). (F) Immunoblot analysis showing inhibition of proliferation is owing to on-target inhibition of FLT3, ERK1/2, and STAT5. Total cell extracts from the AML cells treated with pluripotin for 2 hours were probed with anti-pFLT3, anti-pSTAT5, anti-pERK1/2, anti-FLT3, anti-ERK1/2, and anti-STAT5 antibodies. Representative cell proliferation data and western blottings are shown from 2 independent experiments. Error bars represent ± SD.

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