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ASXL1 and SETBP1 Mutations Affect Cell Viability and Differentiation in AML-MDS

This study examines the impact of ASXL1 and SETBP1 mutations on cell viability, differentiation, and growth rate in AML-MDS. The relative expression of ASXL1 and SETBP1 is analyzed, along with the viability and differentiation of mature and immature cells. Additionally, the study explores the effect of FTY720 and P-PP2A on in vitro and in vivo models. The results reveal distinct changes in cell viability, differentiation, and growth rate in ASXL1 and SETBP1 mutant cells, suggesting their involvement in AML-MDS pathogenesis.

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ASXL1 and SETBP1 Mutations Affect Cell Viability and Differentiation in AML-MDS

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  1. FigureS1 (related to Fig.1) A B

  2. FigureS2 (related to Fig.2) A ASXL1 relative expression Mock/Mock ASXL1-MT/Mock Mock/SETBP1-WT Mock/SETBP1-D868N ASXL1-MT/SETBP1-WT ASXL1-MT/SETBP1-D868N B SETBP1 relative expression Mock/Mock ASXL1-MT/Mock Mock/SETBP1-WT Mock/SETBP1-D868N ASXL1-MT/SETBP1-WT ASXL1-MT/SETBP1-D868N

  3. C Relative viability D * * * ** * * * *

  4. E ①Mock/Mock ②ASXL1-MT/Mock ③Mock/SETBP1-WT ④Mock/SETBP1-D868N ⑤ASXL1-MT/SETBP1-WT ⑥ASXL1-MT/SETBP1-D868N F Mature cells (%) * * ** ** *** Immature cells (%) *** ** * * * * ** ** CD11b MFI ①Mock/Mock ②ASXL1-MT/Mock ③Mock/SETBP1-WT ④Mock/SETBP1-D868N ⑤ASXL1-MT/SETBP1-WT ⑥ASXL1-MT/SETBP1-D868N

  5. FigureS3 (related to Fig.4) A ASXL1 relative expression ASXL1-MT/SETBP1-D868N Mock B SETBP1 relative expression ASXL1-MT/SETBP1-D868N Mock

  6. C *** *** Relative growth rate *** * D

  7. E c-kit Gr1 ScaI CD11b CD34 B220 NGFR =ASXL1-MT FcεRIα SETBP1-D868N (GFP)

  8. FigureS4 (related to Fig.5) A In vitro In vivo - + - + FTY720 P-PP2A P=0.0906 PP2A tublin B

  9. FigureS4 (related to Fig.5) C * * D * * * *

  10. FigureS5 (related to Fig.6) A NES=1.70 P=0.000 AML MDS B NES=1.78 P=0.000 AML MDS C NES=-1.34 P=0.017 AML MDS

  11. D NES=-1.57 P=0.016 AML MDS E NES=-1.13 P=0.071 AML MDS F NES=1.41 P=0.000 AML MDS

  12. G NES=1.42 P=0.021 MDS Control

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