fig6

Identification and targeting of CD22ΔE12 as a molecular RNAi target to overcome drug resistance in high-risk B-lineage leukemias and lymphomas

Figure 6. CD22ΔE12-siRNA liposomal nanoformulation exhibits potent in vivo anti-leukemic activity in NOD/SCID mouse xenograft models of relapsed human BPL. Mice were inoculated i.v. with xenograft cells [(Xeno Case #'s 5 and 10); 4 × 105 cells/mouse] derived from primary leukemia cells of two pediatric patients with relapsed BPL. Sixteen control mice were either left untreated or treated with the liposomal control nanoformulation of scr-siRNA (25 nmol/kg/day × 3 days, day 1-3) or an empty control LNF. Test mice were treated with the LNF of CD22ΔE12-siRNA LNF (low-dose regimen = 2.5 nmol/kg/day × 3 days, day 1-3, n = 10; high-dose regimen = 25 nmols/kg/day × 3 days, day 1-3, n = 9). All 16 control treated mice died and 10 out of 19 CD22ΔE12 siRNA treated mice (pooled both concentrations) were censored alive during the study (Fisher's exact test, 2 tailed, P = 0.0005). CD22ΔE12 treated displayed signifcantly longer time to event observations compared to control mice (median = 190 days for CD22ΔE12 treated vs. median = 107 days for control, Wilcoxon test, one-way Chi-square approximation, P = 0.0012)

Cancer Drug Resistance
ISSN 2578-532X (Online)

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