Fig. 3.
LMP7/PSMB8 is essential for KMT2A-r AML development but dispensable for normal hematopoiesis. A Dot plots depicting % of GFP+ cells in peripheral blood of recipient mice transplanted with 7 × 104 KMT2A::MLLT3 transformed LSKs from LMP7+/+ (n = 12) or LMP7−/− (n = 12) mice over 14 weeks. Two independent cohorts. B Kaplan–Meier survival curves of recipient mice (KMT2A::MLLT3 transformed LSKs from LMP7+/+ (n = 12) or LMP7 −/− (n = 12) mice). Two independent cohorts; Mantel-Cox test. C White blood counts (WBC), hemoglobin (HGB) and platelets (PLT) in the peripheral blood of LMP7−/− (n = 7) for 16 weeks of steady-state hematopoiesis, compared with LMP7+/+ controls (n = 7). D Immunophenotypic quantification of progenitor cell abundance (Prog: Lin− Sca1− c-Kit+), common myeloid progenitors (CMP: Lin− Sca1− c-Kit+ CD34+ FcgR−), granulocyte–macrophage progenitors (GMP: Lin− Sca1− c-Kit+ CD34+ FcgR+) and megakaryocyte-erythroid progenitors (MEP: Lin− Sca1− c-Kit+ CD34− FcgR−) in the bone marrow. E Peripheral blood chimerism over 16 weeks; competitive repopulation assay using BM cells from LMP7−/− (n = 8) or LMP7+/+ (n = 8) donors