Fig. 5: DOT1L inhibition suppresses human TET2 mutated CHIP. | Nature Communications

Fig. 5: DOT1L inhibition suppresses human TET2 mutated CHIP.

From: TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor signaling

Fig. 5

A Number of colonies formed per 1 × 104 CD34+ cells with Cas9-mediated knockout in OR2W5P or TET2 (KO-S or KO-D) in methylcellulose containing DMSO, SGC0946 (SGC) at 1 μM, or ruxolitinib (RUX) at 0.5 μM. Unpaired t test used for significance. B Median fluorescent intensity (MFI) of TPO-R staining minus MFI of isotype control staining on CD34+CD38- cord blood cells at 9 days after nucleofection with Cas9 RNPs targeting OR2W5P or TET2. Cells were treated with DMSO or SGC0946 for 7 days prior to analysis. Unpaired t test used for significance. C Variant allele frequency (VAF) of TET2 mutations in HSPCs enriched from mPB samples cultured in different TPO concentrations for the indicated number of days. Unpaired t test used for significance. D VAF of TET2 mutations in HSPCs from mPB samples cultured with DMSO, SGC0946 at 1 μM, or ruxolitinib at 0.5 μM on day 1 and 14 (n = 3). Unpaired t test used for significance. Data shown are mean ± SD unless otherwise indicated. Asterisks indicate statistical significance. Source data are provided as a Source Data file.

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