Figure 1.
Methionine is a metabolic dependency of AML cells in vitro and in vivo. (A) Relative viable cell number of the AML lines MOLM13 and HL60 grown in amino acid dropout media compared to amino acid complete condition (n = 3). (B) Relative viable cell number of 4 primary AML samples (AML#1-4) divided into the presumed stem (CD34+CD38−) and progenitor (CD34+CD38+) populations and grown on MS5 cells for 7 days in amino acid dropout conditions (n = 4). One AML was entirely CD34+CD38+. (C) EC-50 of AML cell lines grown in a concentration range of methionine (n = 3-5). Effect is the percent stimulation in cell growth with methionine. (D) Relative viability (DAPI−) of healthy CD34+ cells derived from PBMCs (n = 8), normal bone marrow (NBM) (n = 2), cord blood (CB) (n = 4), and from 8 primary AML patient samples (CD34-enriched in the case of NPM1wt AML, mononuclear cells in the case of NPM1cyt AML) (AML#3, 5-11) grown in the absence and presence of methionine for 7 days. (E) Relative viable cell numbers of CD34+ cells derived from NBM and from 8 primary AML patient samples (AML#3, 5-11) grown in the absence and presence of methionine for 7 days. (F) Relative viable cell counts of 3 primary AML samples (AML#10-11, 15) grown in a concentration range of methionase (MGL). (G) Schematic depiction of a MOLM13luc xenograft mouse study in which methionine was depleted from the diet. (H) Bioluminescence examination of AML engraftment performed on day 17 following MOLM13Luc injection. (I) Human CD45 evaluation in peripheral blood samples to assess engraftment on day 14 following MOLM13Luc injection. (J) Kaplan-Meier plot of mouse survival (log-rank test was applied to compare curves). (K) PDX (AML#16) mouse bone marrow (BM) hCD45+ levels (%) at sacrifice. (L) Absolute human cell counts in BM of PDX (AML#16) mouse model. All PDX mice were sacrificed at 1 timepoint. All experiments: error bars represent mean ± standard error of the mean (SEM). Statistical analysis by Student t test or ordinary 1-way analysis of variance, ∗P < .05, ∗∗P < .01, ∗∗∗∗P < .0001.

Methionine is a metabolic dependency of AML cells in vitro and in vivo. (A) Relative viable cell number of the AML lines MOLM13 and HL60 grown in amino acid dropout media compared to amino acid complete condition (n = 3). (B) Relative viable cell number of 4 primary AML samples (AML#1-4) divided into the presumed stem (CD34+CD38−) and progenitor (CD34+CD38+) populations and grown on MS5 cells for 7 days in amino acid dropout conditions (n = 4). One AML was entirely CD34+CD38+. (C) EC-50 of AML cell lines grown in a concentration range of methionine (n = 3-5). Effect is the percent stimulation in cell growth with methionine. (D) Relative viability (DAPI−) of healthy CD34+ cells derived from PBMCs (n = 8), normal bone marrow (NBM) (n = 2), cord blood (CB) (n = 4), and from 8 primary AML patient samples (CD34-enriched in the case of NPM1wt AML, mononuclear cells in the case of NPM1cyt AML) (AML#3, 5-11) grown in the absence and presence of methionine for 7 days. (E) Relative viable cell numbers of CD34+ cells derived from NBM and from 8 primary AML patient samples (AML#3, 5-11) grown in the absence and presence of methionine for 7 days. (F) Relative viable cell counts of 3 primary AML samples (AML#10-11, 15) grown in a concentration range of methionase (MGL). (G) Schematic depiction of a MOLM13luc xenograft mouse study in which methionine was depleted from the diet. (H) Bioluminescence examination of AML engraftment performed on day 17 following MOLM13Luc injection. (I) Human CD45 evaluation in peripheral blood samples to assess engraftment on day 14 following MOLM13Luc injection. (J) Kaplan-Meier plot of mouse survival (log-rank test was applied to compare curves). (K) PDX (AML#16) mouse bone marrow (BM) hCD45+ levels (%) at sacrifice. (L) Absolute human cell counts in BM of PDX (AML#16) mouse model. All PDX mice were sacrificed at 1 timepoint. All experiments: error bars represent mean ± standard error of the mean (SEM). Statistical analysis by Student t test or ordinary 1-way analysis of variance, ∗P < .05, ∗∗P < .01, ∗∗∗∗P < .0001.

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