Evidence for ABL Amplification in Multiple Myeloma and Therapeutic Implications

Figure 3

Copy number abnormalities were detected by FISH in MM cell lines. GLP IGH dual-color breakpoint probe (located at 14q32), P53/1q21 probe (located at 17p13.1/1q21), D13S319/RB1 probe (located at 13q14), GLP C-MYC dual-color breakpoint probe (located at 8q24), and GLP BCR-ABL dual-color fusion probe (located at 22q11/9q34). (a). In interphase FISH of NCI–H929 cells, the image shows three fusion signals indicating IGH amplification (red arrow), as well as two green signals and three orange signals signifying normal p53 performance and 1q21 amplification (yellow arrow). In metaphase FISH, the image shows three green and three orange signals indicating D13S319 and RB1 amplification (potential transformation of chromosome 13 into derivative chromosome 13) (green arrow). (b). LP-1: In interphase FISH, the image shows two fusions, six green signals, and two orange signals indicating IGH rearrangement and amplification (red arrow) as well as three green signals and ten orange signals indicating p53 and 1q21 amplification (yellow arrow). The image shows three green and three orange signals indicating BCR and ABL amplification (blue arrow). In metaphase FISH, the image shows two green and two orange signals on two derivative chromosome 13 (green arrow). (c). In interphase FISH of diploid U266 cells, the image shows one fusion and one orange signal indicating IGH rearrangement and IGH variable region deletion (red arrow). The image displays four green and four orange signals indicating BCR and ABL amplification (blue arrow) as well as four fusion signals indicating c-Myc amplification (pink arrow). In tetraploid cells, two fusion and two orange signals indicate IGH rearrangement and IGH variable region deletion (red arrow). In metaphase FISH, the image shows two green signals and six orange signals indicating p53 deletion and 1q21 amplification (yellow arrow) as well as two green and two orange signals indicating D13S319 and RB1 deletion (green arrow). (d). In metaphase FISH of K562 cells, the image shows two isodicentric Philadelphia chromosomes (yellow arrow), another fusion signal (yellow arrow), three orange ABL (red arrow), and two BCR performances. In interphase FISH, the image shows multiple fusion genes, three orange ABL, and two BCR performances.