ANXA5-associated pathways may influence leukemia progression in human patients. (A) Kaplan-Meier style survival of NSG mice transplanted with 10⁶ THP1 (MLL-AF9⁺) cells and treated with vehicle (blue), ara-C (50 mg/kg, 3 consecutive days as from day 14; purple) or the combination of ara-C (50 mg/kg, 3 consecutive days as from day 14) and celecoxib (50 mg/kg daily from day 10 for 1 week, then once every 3 days; green) (P = .047; P = .07; log-rank test; n = 7) (xenotranplantation model). Median survival for mice treated with vehicle was 40 days, for mice treated with ara-C was 45 days and for mice treated with the combination of ara-C and celecoxib 52 days. The reduced dosing of ara-C was used to allow for testing of possible synergistic effects of ara-C and celecoxib. (B) Kaplan-Meier style survival of NSG mice that received a transplant of 10⁶ Kasumi (AML1-ETO⁺) cells and treated with vehicle (blue), ara-C (50 mg/kg, 3 consecutive days as from day 14; purple) or the combination of ara-C (50 mg/kg, 3 consecutive days as from day 14) and celecoxib (50 mg/kg daily from day 10 for 1 week, then once every 3 days; green) (n = 6) (xenotransplantation model). Due to the large number of mice that survived, median survival could not be defined. (C) Representative immunohistochemistry images of bone sections from healthy individuals, patients with multiple myeloma, B-ALL, and AML stained for ANXA5 (top) or PGE2 (bottom) (P = .009; P = .04; 2-way ANOVA; Tukey test; n = 5 per cohort). The quantification is shown on the right. The scale bar represents 25 μm. (D) Log2 expression of PTGER4, the prostaglandin E2 receptor 4 subtype, in BM cells of healthy individuals (n = 73) or patients with c–/pre–B-ALL t(9;22) (n = 122), pro–B-ALL t(11q23)/MLL (n = 70), or MLL-rearranged AML (n = 38), taken from the BloodSpot portal (Microarray Innovations in Leukaemia study³¹) (P < .0001; 1-way ANOVA; Tukey test).