UM171-driven MYC degradation is essential for its activity on HSCs expansion. (A) Bar graph showing total cell counts after 7 days culture of control (CT), or MYC^WT- or MYC^T58A-transduced CD34⁺ cells in presence or absence of UM171 (35 nM). (B-C) Representative FACS profiles of CD34⁺ (B) and CD34⁺EPCR⁺ (C) subsets in CT or MYC^WT- or MYC^T58A-transduced CD34⁺ CB cells cultured for 7 days in presence of DMSO or UM171 (35 nM). (D) Absolute count of CD34⁺CD45RA⁻CD90⁺EPCR⁺ cell subset in the indicated group (CT, MYC^WT, or MYC^T58A) after 7 days in presence of DMSO or UM171 (35 nM). Representative of 4 independent experiments. Human CD45 engraftment (E), lineage potential (F), and percentage of human CD34⁺ primitive subsets (G) in primary NSG mice transplanted with ex vivo cultured CB cells from the indicated group (outcome of 2 competitive repopulation units) at 16 weeks after transplantation. Human CD45 engraftment (H) and lineage potential (I) in secondary NSG-SGM3 recipients at 8 weeks after transplantation (2-sided Mann-Whitney U test; ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001). See also supplemental Figures 10 and 11.