Novel in vivo model of inducible multi-drug resistance in acute lymphoblastic leukemia with chromosomal translocation t(4;11)

Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Using the t(4;11) ALL line SEM, we evaluated chemotherapy resistance in NOD.CB17-Prkdcscid/J mice. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with phosphate-buffered saline (PBS), or vincristine (0.5 mg/kg body weight) three times per week for 4 weeks (n = 8 per group). The level of P-glycoprotein in SEM cells was increased 3-fold by vincristine treatment compared to PBS-treated mice. Survival curves showed that leukemia cell growth was initially delayed by vincristine treatment, but the mice eventually succumbed to disease. These data describe a novel inducible model for investigating multi-drug resistance mechanisms in high-risk t(4;11) ALL.