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. Author manuscript; available in PMC: 2021 Mar 31.
Published in final edited form as: Nat Cell Biol. 2020 Apr 20;22(6):689–700. doi: 10.1038/s41556-020-0507-y

Fig. 6 ∣. Low-dose DXR treatment reduces the number of persistent pS552-β-cat+ cells from MRD+ human leukaemia.

Fig. 6 ∣

a, Experimental schematic of establishment and treatment of patient-derived xenografts (PDX) (see Methods). be, FACS analysis of diagnostic and day 29 after chemotherapy T-ALL bone marrow samples from MRD+ leukaemia patients. CD45+c-Kit+CD3+ cells (LSCs) expressing pS552-β-cat were enriched 4.4-fold following chemotherapy in patient 57 and 7.3-fold in patient 62. Similar results were obtained from two additional independent biological samples (Extended Data Fig. 6 and Supplementary Table 2). hCD45, human CD45. fk, Diagnostic bone marrow samples were transplanted into NSG recipients (4 × 105 cells each), treated for 5 d with vehicle or low-dose DXR at 2 weeks after transplant, and analysed by FACS for human engraftment. Shown are T-ALL blasts (CD45+c-KitCD3+), LSCs and pS552-p-cat+ LSCs. n = 10 (patient 57 vehicle), 9 (patient 57 low-dose DXR), 5 (patient 62 vehicle) and 7 (patient 62 low-dose DXR) biologically independent mice; data are mean ± s.d. Unpaired two-tailed t-test. ln, Relapsed or refractory adult patients with AML received one cycle of low-dose DNR (6.75 mg m−2 daily for 5 d (days 1–5). Pre-treatment (day 0) and post-treatment bone marrow samples were collected and analysed by FACS. l, Representative FACS plots showing gating strategy for analysis. m,n, LSCs (identified as CD45+CD34+CD38TIM-3+ cells) and pS552-β-cat+ LSCs were quantified according to gating represented in l before and post-low-dose DNR treatment as indicated. n = 10 individual patient samples, pre- and post-treatment samples were analysed individually (m,n).