Interleukin 1 enhances growth factor-dependent proliferation of the clonogenic cells in acute myeloblastic leukemia and of normal human primitive hemopoietic precursors.

Abstract

IL-1 is released by activated monocytes and is thought to be a key mediator of the host immune response. The availability of the purified and, more recently, recombinant IL-1 has allowed the characterization of other biological properties of this molecule. Thus, IL-1 is thought to have the same properties as hemopoietic 1, a growth factor that has been shown to act on primitive murine hemopoietic cells. Here we report that rIL-1 acts synergistically with granulocyte/macrophage CSF (GM-CSF) or granulocyte CSF in the stimulation of clonogenic cells from many patients with acute myeloblastic leukemia (AML). Although IL-1 by itself has no effect on AML blasts, it can support colony formation under conditions where there is detectable production of endogenous GM-CSF. IL-1 also promotes the growth of multipotential progenitors from normal human bone marrow cells in the presence of GM-CSF. These observations support the hypothesis that in the hemopoietic system, IL-1 has a selective effect on primitive precursors.

Nm23-H1 Indirectly Promotes the Survival of Acute Myeloid Leukemia Blast Cells by Binding to More Mature Components of the Leukemic Clone

“…There is evidence that the addition of exogenous rIL6 synergizes with other cytokines, including GM-CSF, IL3, and IL4, to enhance growth and survival of AML cells (30,31). Elevated autocrine/paracrine secretion of IL6 in AML has been shown to constitutively activate Stat3 signaling (32), a feature associated with the upregulation of antiapoptotic proteins, and cyclins that regulate G 1 to S-phase cell cycle transition (33,34).…”

c-KIT expression enhances the leukemogenic potential of 32D cells.

“…In one case the leukaemic cells may produce factors that stimulate the neighboring cells to make growth factors to which the leukemic cells can then respond. For example some human leukaemic cells have been found to produce IL-I which may then induce stromal cells to produce high levels of GM-CSF, G-CSF, and M-CSF (48); these are all factors required for the growth of some leukaemic cells (7,9,(49)(50)(51)(52)(53)(54)(55)(56). This model requires that the leukaemic cells aberrantly express a cytokine and express a receptor for the induced growth factor.…”

“…The growth of human leukaemic cells in tissue culture is dependent upon the presence of specific growth factors (1,2,7,24,42,43). This has led to the suggestion that the growth in vivo is also dependent upon the presence of growth factors.…”

“…Other factors such as IL-1 and IL-6 synergize with the above factors to enhance colony formation (3,6,7). Though colony formation may occur in the absence of added growth factor(s), these cells rarely continue to grow for long periods of time.…”

Pediatric acute myelogenous leukemia cells express IL-6 receptors and are sensitive to a recombinant IL6-Pseudomonas exotoxin

“…[3][4][5][6][7][8][9][10][11] In particular, receptors for IL-6 have been reported on AML cells from adult patients. [5][6][7][8][9] However, there have been no extensive studies of the incidence and levels of IL-6R expression in pediatric AML. Elevated expression by neoplastic cells of cell-surface molecules such as growth factor receptors and differentiation antigens is of particular interest due to the possibility of using these molecules as targets for recombinant ligand-toxins and immunotoxins.…”