Determination of 2A2-miR-29b-ILP treatment and its downstream targets in primary and cell lines of CLL cells. (A) Treatment of ROR1⁺ primary CLL with 2A2-miR-29b-ILP for 24 hours showed twofold higher efficiency of ROR1-targeted uptake of miR-29b than nontargeted IgG-miR-29b-ILP control (P = .015; n = 9). (B) The long-term treatment of 2A2-miR-29b-ILP suppressed the cell viability by ∼10% after 96 hours under the coculture of HS-5 stromal cells (n = 13). (C) 2A2-miR-29b-ILP significantly downregulated DNMT1, DNMT3A, and SP1 compared with 2A2-scramble-ILP control 48 hours posttreatment in primary CLL cells, whereas IgG-miR-29b-ILP exhibited limited effect. (D) mRNA expression of DNMT1, DNMT3A, and SP1 of primary CLL samples from 4 patients revealed significant reduction in each of these mRNAs with 2A2-miR-29b-ILP compared with 2A2-scramble-ILP or IgG-miR-29b-ILP control groups. F29, free-form of miR-29b; n.s., not significant; SC, scrambled miR.