SYNERGISTIC EFFECTS OF INTERLEUKIN-11 WITH OTHER GROWTH-FACTORS ON THE EXPANSION OF HEMATOPOIETIC PROGENITORS FROM NORMAL INDIVIDUALS AND CHRONIC MYELOID-LEUKEMIA PATIENTS RESISTANT TO TREATMENT WITH CYTOSINE-ARABINOSIDE OR EILATIN

Interleukin-11 (IL-11) is a novel cytokine that has been shown to stim ulate human hematopoietic progenitors including the CD34(+) CD33(-) DR (-) early progenitors. IL-11 has little effect on its own but it syner gizes with other hematopoietic growth factors. We investigated the rec overy of human myeloid progenitors incubated with IL-11 alone or in co mbination with other cytokines, including stem cell factor (SCF), inte rleukin-3 (IL-3) and granulocyte macrophage colony-stimulating factor (GM-CSF) following their in vitro treatment with ARA-C (10(-9) M) or E ilatin (10 M). IL-11 in combination with IL-3 and GM-CSF markedly incr eased CFU-C colony growth pre- and post-ARA-C or Eilatin incubation fr om CML and normal individual bone marrow (BM) cells. Similarly, IL-11 alone or in combination with other cytokines increased cell recovery f ollowing 7-day suspension culture. A decrease in BCR/ABL fusion produc t was observed (by FISH analysis) after incubation of BM cells from CM L patients in liquid culture for 7 days with 10(-9) M ARA-C or 10(-7) M Eilatin in the presence of IL-11 alone or in combination with other cytokines. These results indicate that following cytoreductive therapy IL-11 may enhance to a greater extent the growth of normal myeloid pr ogenitors than the malignant clone and may, therefore, be of clinical importance for CML patients treated with chemotherapeutic agents. Copy right (C) 1996 Elsevier Science Ltd.