Post 5-fluorouracil-treated murine bone marrow cells infected with a recombinant retrovirus (murine stem cell virus-interleukin 11 [MSCV-IL-11]) bearing a human IL-11 gene were transplanted into lethally irradiated syngeneic mice. Analysis of proviral integration sites in DNA prepared from hematopoietic tissues and purified cell populations of long-term reconstituted primary and secondary recipients demonstrated polyclonal engraftment by multipotential stem cells. High levels (100-1,500 U/ml) of IL-11 were detected in the plasma of the MSCV-IL-11 mice. Systemic effects of chronic IL-11 exposure included loss of body fat, thymus atrophy, some alterations in plasma protein levels, frequent inflammation of the eyelids, and often a hyperactive state. A sustained rise in peripheral platelet levels (approximately 1.5-fold) was seen throughout the observation period (4-17 wk). No changes were observed in the total number of circulating leukocytes in the majority of the transplanted animals (including 10 primary and 18 secondary recipients) despite a > 20-fold elevation in myeloid progenitor cell content in the spleen. The exceptions were members of one transplant pedigree which presented with myeloid leukemia during the secondary transplant phase. A clonal origin of the disease was determined, with significant expansion of the MSCV-IL-11-marked clone having occurred in the spleen of the primary host. Culturing of leukemic spleen cells from a quaternary recipient led to the establishment of a permanent cell line (denoted PGMD1). IL-11-producing PGMD1 myeloid leukemic cells are dependent on IL-3 for continuous growth in vitro and they differentiate into granulocytes and macrophages in response to granulocyte/macrophage colony-stimulating factor. The inability of autogenously produced IL-11 to support autonomous growth of PGMD1 cells argues against a mechanism of transformation involving a classical autocrine loop.
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1 October 1993
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October 01 1993
Progenitor cell hyperplasia with rare development of myeloid leukemia in interleukin 11 bone marrow chimeras.
R G Hawley,
R G Hawley
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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A Z Fong,
A Z Fong
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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B Y Ngan,
B Y Ngan
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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V M de Lanux,
V M de Lanux
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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S C Clark,
S C Clark
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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T S Hawley
T S Hawley
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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R G Hawley
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
A Z Fong
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
B Y Ngan
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
V M de Lanux
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
S C Clark
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
T S Hawley
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 178 (4): 1175–1188.
Citation
R G Hawley, A Z Fong, B Y Ngan, V M de Lanux, S C Clark, T S Hawley; Progenitor cell hyperplasia with rare development of myeloid leukemia in interleukin 11 bone marrow chimeras.. J Exp Med 1 October 1993; 178 (4): 1175–1188. doi: https://doi.org/10.1084/jem.178.4.1175
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