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Supplemental Figure 1

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Supplemental Figure 2

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Supplemental Figure 3 A B

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OCI-AML3 IgG ControlControl2501000 nM SP2509, 24 h CD86 MOLM13 CD86 Supplemental Figure 4 A B

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MV4-11 SP2509 + PS combination indices SP2509PSFaCI(nM) 5002.50.4630.541 60030.5550.452 7503.750.6180.438 80040.6070.489 9004.50.630.500 100050.7050.399 MV4-11 SP2509 + PS 00.20.40.60.81.0 0 0.5 1.0 1.5 Fractional Effect CI C Supplemental Figure 5 OCI-AML3 SP2509 + PS combination indices SP2509PSFaCI(nM) 50050.2940.927 60060.4860.757 7507.50.6680.666 80080.6590.724 90090.7230.708 1000100.7620.716 MOLM13 SP2509 + PS combination indices SP2509PSFaCI(nM) 50050.3960.759 60060.4670.671 7507.50.4340.963 80080.5840.565 90090.5640.687 1000100.6240.605 A B Primary CD34+ CD38- Lin- AML combination indices SP2509 (nM) PS (nM) FaCI 225100.4040.719 250100.5810.407 500100.570.458 600100.580.449 750100.5980.428 1000100.6350.379 D

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B * OCI-AML3 p21 p16 EZH2 C/EBPα p42 C/EBPα p30 LSD1 SUZ12 β-Actin 250 nM SP2509, 96 h 5 nM PS, 96 h - - + + - + A Supplemental Figure 6

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Supplemental Figure 7 Primary AML SP2509 and PS SP2509 (nM) PS (nM) EffectCI 250.0 10.0 0.466 0.19902 500.0 10.0 0.541 0.10616 600.0 10.0 0.540 0.11361 750.0 10.0 0.567 0.09734 900.0 10.0 0.573 0.10096 1000.0 10.0 0.608 0.07777 A B

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