Effects of granulocyte‐macrophage colony‐stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture

Abstract

We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

Lack of effect of the human GM-CSF analog E21R on the survival of primary human acute myeloid leukemia cells

“…These data are in keeping with those published by others showing GM-CSF responsiveness in primary AML blasts. [16][17][18][19][20][21] In addition to investigating the effects of E21R as a single agent, we have combined it with cytosine arabinoside and did not find any evidence of synergy (Figure 1).…”

“…12 Functional GM-CSF receptors are found on the blast cells of most patients with AML, [13][14][15] and exogenously added recombinant GM-CSF can stimulate proliferation of AML cells. [16][17][18][19][20][21] There is evidence that autocrine production of GM-CSF may play a part in leukemia cell proliferation. 22,23 The profound proapoptotic effects of E21R in all 21 cases of primary AML previously reported raised the possibility that E21R may be very useful in the treatment of AML and prompted us to investigate its effects on AML cell survival and proliferation.…”