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

M. Kiser, J. A. McCubrey, L. S. Steelman, J. G. Shelton, J. Ramage, R. L. Alexander, G. L. Kucera, M. Pettenati, M. C. Willingham, M. S. Miller, A. E. Frankel

Research output: Contribution to journalArticle

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Abstract

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 sarcomaderived 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.

Original languageEnglish (US)
Pages (from-to)814-818
Number of pages5
JournalLeukemia
Volume15
Issue number5
DOIs
StatePublished - 2001

Fingerprint

Myeloid Leukemia
Myeloid Cells
Oncogenes
SCID Mice
Interleukin-3 Receptors
Acute Myeloid Leukemia
src Genes
Myeloid Sarcoma
Diphtheria
Granulocyte-Macrophage Colony-Stimulating Factor
Growth
Intraperitoneal Injections
Nude Mice
Intravenous Injections
Chromosome Aberrations
Lymph Nodes
Cytokines
Kidney
Cell Line
Infection

Keywords

  • Acute myeloid leukemia
  • Cytogenetics
  • Interleukin-3
  • Oncogenes
  • SCID mice
  • TF1

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Kiser, M., McCubrey, J. A., Steelman, L. S., Shelton, J. G., Ramage, J., Alexander, R. L., ... Frankel, A. E. (2001). Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. Leukemia, 15(5), 814-818. https://doi.org/10.1038/sj.leu.2402084

Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. / Kiser, M.; McCubrey, J. A.; Steelman, L. S.; Shelton, J. G.; Ramage, J.; Alexander, R. L.; Kucera, G. L.; Pettenati, M.; Willingham, M. C.; Miller, M. S.; Frankel, A. E.

In: Leukemia, Vol. 15, No. 5, 2001, p. 814-818.

Research output: Contribution to journalArticle

Kiser, M, McCubrey, JA, Steelman, LS, Shelton, JG, Ramage, J, Alexander, RL, Kucera, GL, Pettenati, M, Willingham, MC, Miller, MS & Frankel, AE 2001, 'Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice', Leukemia, vol. 15, no. 5, pp. 814-818. https://doi.org/10.1038/sj.leu.2402084
Kiser M, McCubrey JA, Steelman LS, Shelton JG, Ramage J, Alexander RL et al. Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. Leukemia. 2001;15(5):814-818. https://doi.org/10.1038/sj.leu.2402084
Kiser, M. ; McCubrey, J. A. ; Steelman, L. S. ; Shelton, J. G. ; Ramage, J. ; Alexander, R. L. ; Kucera, G. L. ; Pettenati, M. ; Willingham, M. C. ; Miller, M. S. ; Frankel, A. E. / Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. In: Leukemia. 2001 ; Vol. 15, No. 5. pp. 814-818.
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AU - Kiser, M.

AU - McCubrey, J. A.

AU - Steelman, L. S.

AU - Shelton, J. G.

AU - Ramage, J.

AU - Alexander, R. L.

AU - Kucera, G. L.

AU - Pettenati, M.

AU - Willingham, M. C.

AU - Miller, M. S.

AU - Frankel, A. E.

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N2 - 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 sarcomaderived 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.

AB - 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 sarcomaderived 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.

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KW - Oncogenes

KW - SCID mice

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