Interleukin-11 (IL-11) enhances clonal proliferation of acute myelogenous leukemia cells with strong expression of the IL-11 receptor alpha chain andsignal transducing gp130

We examined the effect of recombinant human interleukin (IL)-11 alone or In combination with various colony-stimulating factors (CSFs), including IL-3 , granulocyte/macrophage (GM)-CSF, granulocyte (G)-CSF, stem cell factor (S CF), flt3 ligand (FL), and thrombopoietin (TPO), on colony formation by leu kemic progenitor cells (L-CFU) obtained from 33 patients with acute myeloge nous leukemia (AML). Leukemic colony formation was found in approximately 7 0 to 80% of the patients in the presence of at least one of the above CSFs. Although IL-11 alone did not support L-CFU, the growth of these progenitor s in the presence of other cytokines was enhanced by IL-11 in 16 out of 33 patients and it showed a synergistic action with G-CSF in 12 of them. This synergistic action occurred in seven out of nine M5 patients (French-Americ an-British (FAB) classification). A single cell clone-sorting experiment cl early demonstrated that this synergistic effect was operative at the single progenitor cell level. The number of leukemic cells proliferating in the p resence of G-CSF+IL-11 was significantly higher than in the presence of G-C SF alone, suggesting that IL-11 recruited dormant leukemic progenitors into the cell cycle. Flow cytometric analysis revealed that all types of AML bl ast cells (M0 similar to M6) ubiquitously expressed gp130, although the lev el of expression was significantly higher In M5 cells. In contrast, express ion of the IL-11 receptor alpha chain (IL-11R alpha) varied between FAB typ es. Blast cells obtained from M1, M3 and M5 patients showed higher levels o f expression, with M5 cells showing the strongest expression, interestingly , the leukemic progenitor cells for which proliferation was synergistically enhanced by IL-11 had significantly higher expression of both IL-11R alpha and gp130. These results suggest that administration of IL-11 in vivo may stimulate the proliferation of leukemic progenitor cells, particularly M5 c ells, in the presence of G-CSF, and that the responsiveness of L-CFU to IL- 11 may be predicted by a simple receptor assay.