Extended Data Fig. 3: Fatty acid metabolism can be inhibited by MCL-1 inhibitors.

MCL-1 inhibition decreases fatty acid metabolism in ven/aza resistant LSCs. a. Relative expression of ACADVL in siRNA knockdown samples N = 4 independent patient samples. Data are presented as mean values + /- SD. Significance was measured by paired two-tailed Student’s t-test. b. Basal respiration in ACADVL siRNA knockdown cells with or without VU and VU + Aza. N = 3 patient specimens with N = 5 technical replicates for each experiment. Data are presented as mean values. Patient samples run as single experiment with 3 unique patients. c. SiRNA knockdown of ACADVL and viability with or without VU and VU + Aza. N = 3 independent patient samples for each experiment. Data are presented as mean values + /- SD. Significance was measured by unpaired two-tailed Student’s t-test. d. Global metabolite measurement in sensitive and resistant LSCs after VU + Aza treatment relative to control. N = 6 independent patient specimens versus N = 3 sensitive patient specimens measured across 4 technical replicates per patient sample. Heat map shows the ratio of VU660103 treated to untreated control. e. Global carnitine and fatty acid levels after 4 h of VU + Aza in ven/aza resistant (R) and sensitive (S) specimens. Metabolites that show selective decrease upon drug treatment in ven/aza resistant specimens are indicated by a red X. N = 6 independent patient specimens versus N = 3 sensitive patient specimens measured in across 4 technical replicates per patient sample.

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