Patient myeloma cells treated in whole bone marrow cell–mixed culture are selectively killed by chaetocin in comparison to other bone marrow leukocytes, and chaetocin has in vivo antimyeloma activity. (A-C) Unsorted bone marrow leukocytes obtained from 4 patients with multiple myeloma were treated with 100 nM chaetocin or diluent for 24 hours and subjected to FACS analyses examining cell death in various leukocyte subpopulations. Myeloma cells were readily killed by chaetocin (A; representative data shown), and combined granulocytes and monocytes (B; representative data shown) were relatively spared. Results from 4 unsorted patient marrow leukocyte samples are indicated in panel C, with surviving cells defined as those with low annexin and 7-AAD staining. (D) Chaetocin has in vivo antimyeloma activity in established RRMI 8226 SCID flank xenograft mouse tumors. Arrows indicate times of intraperitoneal chaetocin administration, whereas * indicates statistically significant differences from corresponding vehicle control values (P < .05). The control group consisted of 10 animals, and treatment groups consisted of 6 animals each.