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

• Published in: Leukemia Vol. 15; no. 5; pp. 814 - 818
• Main Authors: KISER, M, MCCUBREY, J. A, FRANKEL, A. E, STEELMAN, L. S, SHELTON, J. G, RAMAGE, J, ALEXANDER, R. L, KUCERA, G. L, PETTENATI, M, WILLINGHAM, M. C, MILLER, M. S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.05.2001; Nature Publishing Group
• Subjects: Abl protein; Abnormalities; Acute myeloid leukemia; Animal tumors. Experimental tumors; Animals; BCR protein; Biological and medical sciences; Cells; Chromosome Aberrations; Colony-stimulating factor; Cytogenetics; Cytokines; Diphtheria; Experimental malignant blood diseases; Female; Fusion protein; Genes, src - physiology; Genetic aspects; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Growth factors; Health aspects; Hematologic and hematopoietic diseases; Humans; Injection; Inoculation; Interleukin 3; Intravenous administration; Kidneys; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph nodes; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, SCID; Oncogenes; Organs; Receptors; Receptors, Interleukin-3 - analysis; Sarcoma; Signal transduction; Src protein; Tumor Cells, Cultured; Tumors; United States; United States > US; Animal model; Acute; Cytokine; Rodentia; Malignant hemopathy; Heterograft; Genetic transfer; Vertebrata; Mammalia; Mouse; Interleukin 3; SCID mouse; Animal; C-Onc gene; Established cell line; Engraftment; Graft; Tumor cell; Protooncogene; Acute myelocytic leukemia; Biological receptor
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402084

We have developed an in vivo model of differentiated human acute myeloid leukemia (AML) by retroviral infection of the cytokine-dependent AML cell line TF-1 with the v-Src oncogene. When injected either intravenously or intraperitoneally into 300 cGy irradiated SCID mice, animals formed multiple granulocytic sarcomas involving the adrenals, kidneys, lymph nodes and other organs. 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 express interleukin-3 receptors and remained sensitive to the diphtheria fusion protein DT388IL3. Further, these granulocytic sarcoma-derived cells grew again in irradiated SCID mice (n = 10). The cytogenetic abnormalities observed prior to inoculation in mice were stably present after in vivo passage. Similar to the results with v-Src transfected TF-1 cells, in vivo leukemic growth was observed with TF-1 cells transfected with the human granulocyte-macrophage colony-stimulating factor gene (n = 5) and with TF-1 cells recovered 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) did not grow in irradiated SCID mice. This is a unique, reproducible model for 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.