Extended Data Fig. 2: PTPN11 confers metabolic alterations leading to venetoclax resistance.

Effects of PTPN11 mutation on metabolism and venetoclax sensitivity. a. Measurement of fatty acids in ven/aza sensitive and resistant LSCs from lipodomics analysis shown as box and whiskers plot with min and max represented. N = 3 sensitive patient specimens versus N = 3 resistant patient specimens measured across 4 technical replicates per patient sample. Significance was measured by paired two-tailed Student’s t-test. b. Venetoclax and ven/aza viability of primary AML cells of patients with or without a PTPN11 mutation. N = 3 independent patient wild-type specimens versus N = 2 (venetoclax + aza) or 3 (venetoclax alone). PTPN11 resistant patient specimens measured across 3 technical replicates per patient sample. Data are presented as mean values. c, d. Basal respiration and glycolytic rate of primary AML cells transduced with lentiviral PTPN11 E76A mutation. N = 1 independent patient wild-type specimens versus N = 1 PTPN11 mutant patient specimens measured across 4-5 technical replicates per sample. Individual values in glycolytic rate consolidated in instrument software and mean value shown. Data are presented as mean values. Patient sample run as single experiment with single transduction.

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