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In vitro effects of interleukin-12 on the growth of blast progenitors in acute myelogenous leukemia

Leukemia volume 15, pages 1996–1998 (2001)Cite this article

Interleukin-12 (IL-12) is a cytokine that is thought to play a central role in cell-mediated immunity and also regulate hematopoiesis.1,2 In the lymphoid system, it acts primarily on natural killer (NK) and T cells and induces them to secrete cytokines, particularly interferon-γ (IFN-γ), augments NK cell cytotoxicity leading to generation of lymphokine-activated killer cells, stimulates the proliferation and activity of cytotoxic T cells, and promotes the development of T-helper type 1 (Th1) cells. IL-12 exhibits antitumor activity against a variety of cell lines, xenografts of solid tumors and primary leukemic blasts when used with IL-2 or cytotoxic drugs. IL-12 is also known to act synergistically with hematopoietic growth factors (HGFs), including interleukin-3 (IL-3) and stem cell factor (SCF), to promote the growth and differentiation of hematopoietic precursors.3,4 This suggests another potential usefulness of IL-12 in clinical medicine but raises concerns as to whether IL-12 might have adverse effects on leukemia patients by stimulating leukemia cell growth.

The blast cells in acute myelogenous leukemia (AML) are thought to be derived from small population of cells called ‘blast progenitors’ that possess high growth capacity.5 Upon growth stimulation, blast progenitors undergo either self-renewal or a series of terminal divisions that lead to the generation of a large population of descendant blasts having modest proliferative ability. Self-renewal is the process that maintains leukemic progenitors and causes their unlimited growth, and a correlation has been demonstrated between the high self-renewal capacity of blast progenitors and poor clinical outcome. Since the effect of IL-12 on the proliferation and self-renewal of blast progenitors in AML has not been described in detail, the in vitro effects of IL-12 on myeloid leukemia cells were investigated in this study.

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Acknowledgements

The author thanks Dr K Toyama, First Department of Internal Medicine, Tokyo Medical college, for providing patient samples and T Minegishi for assistance in cell culture.

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  1. Department of Clinical Laboratory, National Children's Hospital, Tokyo, Japan

    J Miyauchi

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Miyauchi, J. In vitro effects of interleukin-12 on the growth of blast progenitors in acute myelogenous leukemia. Leukemia 15, 1996–1998 (2001). https://doi.org/10.1038/sj.leu.2402308

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