Fig. 2: Induction of cell differentiation in all subtypes of AML cells by CM-444 and CM-1758.
From: Epigenetic-based differentiation therapy for Acute Myeloid Leukemia
A Cell differentiation assay measuring CD11b by flow cytometry in a panel of 15 AML cell lines belonging to different subtypes (M1 to M7, according to FAB classification). Cells were treated daily with 25% GI50 of each compound for 48 h. ATRA was used as the differentiation therapy reference. The data shown are the mean of three biologically independent experiments. B CD11b and annexin-V were measured by flow cytometry at 2, 4, 6, and 8 days after treating HL-60 and ML-2 cell lines daily with CM-444 or CM-1758. Data are presented as mean values +/- S.D. of three biologically replicates. C Cell differentiation assay measuring CD11b by flow cytometry in eight primary AML patient samples. Samples were treated daily with 500 nM and 2 µM of each compound for 48 h. D GSEA enrichment analysis showing negative regulation of a MYC related gene set and positive regulation of a GFI1, a GATA2, or a CEBPA-related gene set in ML-2 and HL-60 cells after treatment with CM-444 or CM-1758. HL-60 and ML-2 cell lines were treated with CM-444 or CM-1758 daily for 48 h. Then, E q-polymerase chain reaction (PCR) of MYC, CDKN2A (p16) and CDKN1A (p21); F Cell-cycle analysis; G q-PCR of GATA2, SPI1 (PU.1), TAL1 (SCL) and CEBPA and H May–Grünwald–Giemsa staining performed in HL-60 and ML-2 cell lines after CM-444 and CM-1758 treatment. Scale bar, 10 µm. Data are presented as mean values +/- S.D. of three biologically replicates. Source data are provided as a Source data file.
