Figure 5.
Figure 5. Pharmacological inhibition of PRMT1 reduces FLT3-ITD+ AML growth and survival. (A) Western blotting analysis of FLT3 R972/973 me2a in MV4-11 cells treated with the indicated doses of MS023 (left panel). Quantitative analysis of R972/973 me2a levels based on ImageJ software (right panel). (B) Viability of MV4-11 cells treated with the indicated doses of MS023, based on a CellTiter Glo assay. **P < .01, ***P < .001 vs vehicle. (C) CD34+ cells from FLT3-ITD+ AML (n = 11) were treated for 5 days with MS023 at various doses. Basal FLT3 R972/973 me2a levels are shown (left panels). Linear regression analysis of those R972/973 me2a levels and MS023 50% inhibitory concentration (right panel). Correlation was calculated as an R value, and significance was determined by Pearson correlation. (D) CFC assay of primary FLT3-ITD+ AML (n = 5) CD34+ cells treated with 5 µM MS023 or vehicle. *P < .05, **P < .01. (E) Western blotting analysis of FLT3 R972/973 me2a in MV4-11 cells treated with the indicated doses of TC-E-5003. (F) CFC assay of primary FLT3-ITD+ AML (n = 4) CD34+ cells treated with 3 µM TC-E-5003 or vehicle. **P < .01, ***P < .001. Results represent mean ± SD.

Pharmacological inhibition of PRMT1 reduces FLT3-ITD+ AML growth and survival. (A) Western blotting analysis of FLT3 R972/973 me2a in MV4-11 cells treated with the indicated doses of MS023 (left panel). Quantitative analysis of R972/973 me2a levels based on ImageJ software (right panel). (B) Viability of MV4-11 cells treated with the indicated doses of MS023, based on a CellTiter Glo assay. **P < .01, ***P < .001 vs vehicle. (C) CD34+ cells from FLT3-ITD+ AML (n = 11) were treated for 5 days with MS023 at various doses. Basal FLT3 R972/973 me2a levels are shown (left panels). Linear regression analysis of those R972/973 me2a levels and MS023 50% inhibitory concentration (right panel). Correlation was calculated as an R value, and significance was determined by Pearson correlation. (D) CFC assay of primary FLT3-ITD+ AML (n = 5) CD34+ cells treated with 5 µM MS023 or vehicle. *P < .05, **P < .01. (E) Western blotting analysis of FLT3 R972/973 me2a in MV4-11 cells treated with the indicated doses of TC-E-5003. (F) CFC assay of primary FLT3-ITD+ AML (n = 4) CD34+ cells treated with 3 µM TC-E-5003 or vehicle. **P < .01, ***P < .001. Results represent mean ± SD.

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