Figure 6.
The KDM6B inhibitor GSK-J4 in mouse and human samples improved hematopoiesis. (A) Effect of GSK-J4 (0.5 µM) on bone marrow (BM) repopulation capacity, based on G2 colony-forming units in serial methylcellulose colony formation assays using BM LSKs isolated from old, age-matched mice (aged >70 weeks; WT mice: N = 5 treated with control, N = 5 treated with GSK-J4; Vav-KDM6B mice: N = 7 treated with control, N = 7 treated with GSK-J4). (B) Effect of GSK-J4 (0.5 µM) treated and LPS on BM repopulation capacity, based on G2 colony-forming units in serial methylcellulose colony formation assays using LSK BM cells isolated from old, age-matched mice (WT mice: N = 9 control, N = 8 GSK-J4 only, N = 9 LPS only, N = 9 LPS plus GSK-J4; Vav-KDM6B mice: N = 13 control, N = 13 GSK-J4 only, N = 10 LPS only, N = 10 LPS plus GSK-J4). (C-D) Effects of GSK-J4 (160 µg/week for 4 weeks) on whole BM cell counts of WT mice and on PB chimerism in recipient mice (WT mice: N = 3 control, 4 GSK-J4 only, N = 4 LPS only, N = 5 LPS plus GSK-J4; Vav-KDM6B mice: N = 4 control, N = 4 GSK-J4 only, N = 4 LPS only, N = 3 LPS plus GSK-J4). (E) Effect of GSK-J4 (0.5 µM) on hematopoiesis in low-risk MDS, based on colony-forming units in methylcellulose colony formation assays using primary MDS BM CD34-positive cells isolated from patients with untreated low-risk MDS (N = 11). All error bars are based on ± SEM.