Fig. 2: Sensitivity toward therapeutic NHE1 inhibition in different AML subtypes.

A Kasumi-1, MOLM-13, and MV4-11, but not other human AML cell lines, showed higher NHE1 activity and were sensitive to amiloride (10 μM) and HMA (10 μM) (n = 5). B Kasumi-1, MOLM-13, and MV4-11 (amiloride-sensitive AML) showed higher level of NHE1 phosphorylation compared to THP-1, OCI-AML3, and KG-1 (amiloride-resistant AML) (n = 3) (see also Supplementary Fig. S1A for the western blot analysis). C Heatmap summarizing the effects (fold changes of growth, pHi, apoptosis, and proliferation normalized to vehicle control) of in vitro amiloride treatment on different human AML cell lines (n = 4) (see Supplementary Fig. S1B–E for the raw data to the heatmap). D Level of NHE1 phosphorylation significantly correlated with the area-under-curve (AUC) of amiloride treatment in different human leukemic cell lines (n = 10). E–H Primary AML samples with FLT3, RAS, or KIT mutation showed E higher level of NHE1 phosphorylation (n = 30), F increased sensitivity toward in vitro amiloride treatment (n = 29), G intracellular acidification upon in vitro amiloride treatment (n = 21), and H increased apoptosis induction upon in vitro amiloride treatment (n = 21), compared to WT samples. I Level of NHE1 phosphorylation significantly correlated with the AUC of amiloride treatment in primary AML samples (n = 25). Amiloride concentration was 10 μM in these experiments.