Effects of interleukin‐5 on acute myeloid leukemias

Abstract

Because of the known activity of interleukin-5 (IL-5) as a growth factor for human eosinophils, we performed studies to ascertain whether M4Eo acute leukemia cells might be capable of responding to IL-5. Surprisingly, short term incubation of freshly isolated M4Eo blasts with rhIL-5 induced differentiation of the cells to macrophages. To determine whether other variants of acute myelogenous leukemia (AML) might also be capable of responding to IL-5, we studied cells from four additional unselected cases and found that one responded to IL-5 by vigorous proliferation. Using biotinylated rhIL-5, second labelling with streptavidin-fluorescein isothiocyanate (FITC) and flow cytometric analysis, specific binding of IL-5 to both responsive leukemias was demonstrated, suggesting the presence of specific IL-5 receptors. Additional study will be needed to assess the frequency of IL-5 responsiveness in AML and to determine the relationship of these phenomena to the physiologic role of IL-5 in the regulation of hematopoiesis.

Expression of interleukin‐5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype

“…Finally in this series, 14 cases had eosinophilia documented at 0.5-2 1.0% of cells: 12 of these cases were IL-SR positive. These data accord with the observation that leukaemic cells from most cases of AML with t(8;21) or structural abnormalities of chromosome 1 6 can differentiate in response to IL-5 in vitro (Le Beau et al, 1983;Ema et al, 1990;Baumann et al, 1992). We confirmed this and observed that the morphological differentiation included eosinophils (Fig 2).…”

Inflammatory response mediates cross-talk with immune function and reveals clinical features in acute myeloid leukemia

“…In addition, we observed more eosinophilic infiltration in the low-inflammatory response group. Studies have shown that IL5 can induce an increase in the number of eosinophils in AML [ 44 , 45 ]. When we compared the differences in the expression of pro- and anti-inflammatory genes, we found that the expression level of IL-5 was higher in the low-inflammatory group compared to the high-inflammatory group.…”

Hematopoietic Growth Factors and Blast Progenitors in Acute Leukemia

“…Differences in the effects of HGFs on AML blast progenitors can also be detected in other ways. As mentioned above, leukemic stem cells in AML that are stimulated to proliferate, undergo either a self-renewal (birth) or a determination (death) process during cell divi- Thrombopoietin, TPO (c-mplligand) growth stimulation (not restricted to AML-M7) [123][124][125][126][127] autocrine growth stimulation [166) growth enhancement with other cytokines [125,127) induction of megakaryocytic differentiation [123,124) Erythrpoietin, EPO no growth stimulation on its own [128,129) growth stimulation of erythroid leukemia cells [130) growth enhancement with other cytokines (not restricted to AML-M6) [128,129] Flt3 ligand, FL growth stimulation [111,112] synergistic growth enhancement with other cytokines [ [119][120][121][122] induction of differentiation towards eosinophils in sorne patients with AML-M2 [120,121] or AML-M6 [119] induction of monocytic differentiation [122] IL-6 little growth stimulation on its own [89,100,113,114] growth stimulation or inhibition in sorne patients [87,100,150] indirect growth stimulation [168] enhancement [87,89,100,[113][114]…”

“…The ability of these HGFs to induce differentiation or proliferation of AML blasts progenitors is variable. IL-5 has been shown to rarely induce maturation of AML blasts into eosinophils or macrophages [119][120][121][122] in patients with AML, including AML-M2 (FAB classification) with chromosomal translocation (8;21). TPO induces only minimal incomplete differentiation of blasts of the megakaryocytic lineage along the megakaryocyte pathway [123,124], and stimulates the growth of blast progenitors in a small population of AML patients, irrespective of the FAB classification subtype [123 -127].…”