A B Figure S1 (related to Figure 1). BETi-tolerant A375 and NOMO-1 cells show an abrogated apoptotic response to BETi. C D E F.

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A B Figure S1 (related to Figure 1). BETi-tolerant A375 and NOMO-1 cells show an abrogated apoptotic response to BETi. C D E F

A Log 2 FC -3 3 A375A375-t1A375-t2 CPI203 vs. DMSO Tolerant vs. Parental CPI203 NOMO-1 CPI203 CPI203 vs. DMSO Tolerant vs. Parental NOMO-1-t A375A375-t1A375-t2 CPI203 vs. DMSO NOMO-1 NOMO-1-t CPI203 vs. DMSO A375 A375-t1 A375-t2 BCL2L1 GAPDH A375 A375-t1 A375-t2 LP-1 BCL2 GAPDH B C BCL2L1 BCL2 Vinculin Figure S2 (related to Figure 1). BETi-tolerant A375 and NOMO-1 cells show increased expression of BCL2 family genes.

A C D B E Clone 2 Clone 10 Vector BCL2L1  -actin F Figure S3 (related to Figure 2). Increased expression of BCL2 family members is important for the BETi tolerance phenotype.

A CD % depolarization, BAD peptide% depolarization, HRK peptide Cell linemeanSEMPmeanSEMPBCL2, RMABCL2L1, RMA MV Kasumi NCI-H Daudi SUDHL SUDHL B Figure S4 (related to Figure 4). Basal expression of apoptotic factors is predictive of response to BETi.

p < p = 0.03p = p = 0.06p = 0.02 A BCD p = 0.03 p < high low high low high low high low Figure S5 (related to Figure 4). Basal expression of apoptotic factors is predictive of response to BETi.

STD lowOPM2DOHH2K562Kasumi-1MOLM13RajiSUDHL4STD highTHP-1WSU-DLCL2SUDHL5LP1MV-411MC116REH BCL2L1 NamalwaMOLT4MOLT16ML2KMS26HL60Daudi CA46KARPAS422KMM1KMS27MOLP8H929PL21RPMI8226SET2U266 BCL2 cell line BCL2, ng/  g lysate BCL2L1, ng/  g lysateBCL2/BCL2L1 GI50,  M KARPAS KMS DOHH MOLM SUDHL PL Opm MV THP HL ML Kasumi REH WSU-DLCL MOLT Raji LP MOLP CA KMM RPMI H MC U KMS Namalwa SUDHL MOLT SET K Daudi A B C STD lowSTD high STD lowSTD high STD lowSTD high STD low STD high Figure S6 (related to Figure 4). Basal expression of apoptotic factors is predictive of response to BETi.