a, b, Summary of pediatric leukemia patients analyzed by FACS for LSCs and pS552-β-cat+ LSCs. B- and T-lymphoid LSCs were identified as enriched in CD45+ CD34+ CD19+ and CD45+ c-Kit+ CD3+ cells, respectively. BM samples at diagnosis and at day 29 post-chemotherapy treatment. Pt samples 019 and 034, B and T-lymphoid leukemias exhibiting chemoresistant pS552-β-cat+ LSCs, were subjected to further in vivo treatment and analysis. Pt 024 and 031, B and T-lymphoid acute leukemias lacking chemoresistant pS552-β-cat+ LSCs, were also tested. c, Experimental schematic of establishment and treatment of patient-derived xenografts (PDX) (see Methods). d, e, Kaplan-Meier survival curve of 1° PDX recipients of diagnostic and post-chemotherapy BM from Pt 019 (d) and Pt 034 (e). n=3 biologically independent replicates each. f, g, Kaplan-Meier survival curve for 2° PDX recipients treated with vehicle or low-dose nanoDXR. BM from 1° recipients of diagnostic (d) or post-chemotherapy (e) was transplanted into 2° PDX recipients and treated with low-dose NanoDXR 14 days post-transplant. h, i, FACs analysis of 2° PDX recipient BM from (f-g). Human CD45+ and human LSC engraftment was determined after succumbing to leukemia or at experimental endpoint. n=10 (each, h) and n=10 and 9 (vehicle and low-dose NanoDXR, respectively, i) biologically independent replicates; mean ± SEM is indicated. Statistics determined by unpaired two-tailed t-test. j–o, Similar analysis to D-I but of patient-derived xenografts (PDX) from Pt 024 and Pt 031, which lack chemoresistant pS552-β-cat+ LSCs. n=3 biologically independent replicates each (j-k). n = biologically independent replicates as indicated (f, g, l, m). n=9,10 (vehicle and low-dose NanoDXR, respectively, n) and n=10,9 (vehicle and low-dose NanoDXR, respectively, o) biologically independent replicates; mean ± SEM is indicated. Statistics determined by unpaired two-tailed t-test. (N.S. = not significant). Statistics determined by Log-rank (Mantel-Cox) test for survival curves.