Nilotinib reduces genomic damage and instability caused by melphalan. (A-B) MM cells were treated with DMSO only (D), melphalan (M), nilotinib (N), or a combination of both drugs (M+N) for 48 hours and evaluated for DNA breaks (by measuring γ-H2AX level) (A) and genomic instability (using micronucleus assay) (B-C). A representative flow cytometry image of micronuclei in MM.1S cells (B) and bar graphs showing percent micronuclei in 3 MM cell lines (C) are shown. Error bars indicate SDs of 3 independent experiments, and 2-tailed P values are derived by t test (∗P < .05). (D) MM.1S cells treated with nilotinib (N; 2.5 μM), low dose melphalan (M; 1 μM), or combination were cultured for 3 weeks. DNA from the cultured and “day 0” (baseline control) cells was analyzed using SNP arrays (Affymetrix). Copy number events in cultured cells were identified using the genome of “day 0” cells as a baseline. A copy number event was defined as a change in ≥3 consecutive probes by 1 copy. Images showing amplifications (red dots) and deletions (blue dots) on all chromosomes and bar graph showing total copy number change events throughout genome. DMSO, dimethyl sulfoxide; SD, standard deviation.