Steps for improved outgrowth and maintenance of the genetic signature of human diagnostic leukemia samples in humanized “ossicles,” which mimic the natural niche in vivo. Immune-deficient mice were implanted subcutaneously with calcified scaffolds previously seeded with human MSCs. Six to 8 weeks later, diagnostic leukemia cells (CD34⁺ purified or T cell–depleted) were injected. Tumors were explanted and leukemia cells transferred to ossicles in secondary recipients. This technique was shown to result in a better engraftment rate of leukemia samples with favorable risks than the traditionally used IV administration technique. In addition, the self-renewal and genetic profile of the original leukemia was better maintained. Professional illustration by Somersault18:24.