Successful engraftment by leukemia initiating cells in adult acute lymphoblastic leukemia after direct intrahepatic injection into unconditioned newborn NOD/SCID mice

Abstract

Xenogeneic transplantation has been the gold standard for enumeration of leukemia initiating cells in acute myeloid and lymphoblastic leukemia (ALL). Most transplantation models have required conditioning in which the recipients were either irradiated or treated with chemotherapy prior to injection of human leukemia cells. In this study, we reported an undescribed model in which adult ALL cells were injected into unconditioned newborn nonobese diabetic severe combined immunodeficient mice via an intrahepatic route. Bone marrow (BM) and peripheral blood were collected from patients with ALL at diagnosis or relapse. CD34(+) selected lymphoblasts or mononuclear cells were transplanted as mentioned previously. Cells were also transplanted into sublethally irradiated adult mice via intravenous route for comparison. Leukemia engraftment was enumerated from mouse BM 6 to 18 weeks after transplantation. Clonality of the engrafting cells was examined based on IGH rearrangement and fluorescent in situ hybridization. Five of 13 ALL samples engrafted into the recipient BM 6 to 18 weeks after transplantation. Engrafted cells recapitulated the immunophenotype and cytogenetic characteristics of the original samples. Engraftment in BM and peripheral blood was significantly correlated. Importantly, there was significant correlation of engraftment between this and the conventional adult nonobese diabetic severe combined immunodeficient mouse model involving irradiation. Our results demonstrated that this unconditioned newborn mouse model could be used for enumeration of leukemia initiating cells in ALL and should be further evaluated.