Inhibition of ABL1 by shRNA or nilotinib reduces genomic instability in MM cells. (A-B) ABL1 was inhibited in MM cell lines (MM.1S and RPMI8226) either using shRNA (C, control; sh-ABL1, ABL1-shRNA) (A) or by culturing in the presence of DMSO or 5 μM ABL1 inhibitor (nilotinib) for 48 hours (B), and cells were evaluated for genomic instability using the micronucleus assay. Flow cytometry images of micronuclei (Ai,Bi) and bar graphs showing relative fold change in micronuclei (Aii,Bii) are shown. Error bars indicate SDs of 3 independent experiments; 2-tailed P values are derived by t test (∗P < .05-.001; ∗∗P < .001). (C) RPMI8226 cells were treated with DMSO only (control) or nilotinib for 21 days, and acquisition of new copy number events relative to the baseline genome of “day 0” cells was evaluated using SNP6.0 arrays (Affymetrix). Representative image of copy number events (amplifications, red dots; deletions, blue dots) on chromosomes 4 and 9 and bar graph showing copy events over whole genome are shown. DMSO, dimethyl sulfoxide; SD, standard deviation.