Extended Data 3:

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 hours 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.