Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice

We have developed an in vivo model of differentiated human acute myeloid le ukemia (AML) by retroviral infection of the cytokine-dependent AML cell lin e TF-1 with the v-Src oncogene. When injected either intravenously or intra peritoneally into 300 cGy irradiated SCID mice, animals formed multiple gra nulocytic sarcomas involving the adrenals, kidneys, lymph nodes and other o rgans. The mean survival time was 34 +/- 10 days (n = 40) after intravenous injection and 24 +/- 3 days (n = 5) after intraperitoneal injection of 20 million cells. The cells recovered from leukemic animals continued to expre ss interleukin-3 receptors and remained sensitive to the diphtheria fusion protein DT388ILS. Further, these granulocytic sarcoma-derived cells grew ag ain in irradiated SCID mice (n = 10). The cytogenetic abnormalities observe d prior to inoculation in mice were stably present after in vivo passage. S imilar to the results with v-Src transfected TF-1 cells, in vivo leukemic g rowth was observed with TF-1 cells transfected with the human granulocyte-m acrophage colony-stimulating factor gene (n = 5) and with TF-1 cells recove red from subcutaneous tumors in nude mice (n = 5). In contrast, TF-1 cells expressing v-Ha-Ras (n = 5), BCR-ABL (n = 5), or activated Raf-1 (n = 44) d id not grow in irradiated SCID mice. This is a unique, reproducible model f or in vivo growth of a differentiated human acute myeloid leukemia and may be useful in the assessment of anti-leukemic therapeutics which have human- specific molecular targets such as the interleukin-3 receptor.