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. Author manuscript; available in PMC: 2023 Sep 1.
Published in final edited form as: Cell Metab. 2021 Mar 25;33(5):1027–1041.e8. doi: 10.1016/j.cmet.2021.03.003

Figure 6. ME2-mediated fumarate sensing supports leukemia growth.

Figure 6.

(A–C) Growth curves of stable MOLM14 cells were determined (A). Cells were treated with PRMT1i and DMF. Cell viability was determined by cell counting after 4 days of culture (B). Colonies of MOLM14 cells were counted 7 days after treatment (C).

(D) ME2-knockdown and re-expression MOLM14 cells were transplanted into sublethally irradiated NSG mice to monitor leukemia progression (n = 5).

(E–O) ME2 (E) and PRMT1 (F) protein in normal and leukemic human BM samples were determined. R67 methylation of immunoprecipitated ME2 was determined (G). ME2 activity was assayed in the presence of fumarate (H). MRPL45 (I), MT-CO1 (J), and MT-ND6 (K) were quantified by western blotting. mtDNA was quantified by qPCR (L). Pearson’s correlation of ME2 protein with MT-CO1 (M), MT-ND6 (N), and mtDNA abundance (O) in AML samples was determined.

(P) Working model of ME2-mediated fumarate signaling.

Data are presented as mean ± SEM from three independent experiments. *p < 0.05, **p < 0.01; n.s. indicates not significant. See also Figure S6.