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 stimulate human hematopoietic progenitors including the CD34+ CD33- DR- early progenitors. IL-11 has little effect on its own but it synergizes with other hematopoietic growth factors. We investigated the recovery of human myeloid progenitors incubated with IL-11 alone or in combination with other cytokines, including stem cell factor (SCF), interleukin-3 (IL-3) and granulocyte macrophage colony-stimulating factor (GM-CSF) following their in vitro treatment with ARA-C (10(-9) M) or Eilatin (10(-7) M). IL-11 in combination with IL-3 and GM-CSF markedly increased CFU-C colony growth pre- and post-ARA-C or Eilatin incubation from CML and normal individual bone marrow (BM) cells. Similarly, IL-11 alone or in combination with other cytokines increased cell recovery following 7-day suspension culture. A decrease in BCR/ABL fusion product was observed (by FISH analysis) after incubation of BM cells from CML 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 progenitors than the malignant clone and may, therefore, be of clinical importance for CML patients treated with chemotherapeutic agents.
Einat
M
M
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
Nagler
A
A
Amiel
A
A
Fejgin
M D
MD
Rudi
A
A
Kashman
Y
Y
Fabian
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy; D010618:Phenanthrolines / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D017370:Interleukin-11; D007377:Interleukin-3; D010618:Phenanthrolines; D019089:Stem Cell Factor; D003561:Cytarabine; C097538:eilatine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor