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.

Abstract

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.

• Authors: M Einat, A Nagler, A Amiel, M D Fejgin, A Rudi, Y Kashman, I Fabian
• Journal: Leukemia research (Leuk Res) Vol. 20 Issue 9 Pg. 751-9 (Sep 1996) ISSN: 0145-2126 [Print] England
• PMID: 8947585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interleukin-11
• Interleukin-3
• Phenanthrolines
• Stem Cell Factor
• Cytarabine
• eilatine
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• CHO Cells
• Cricetinae
• Cytarabine (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Drug Synergism
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Hematopoietic Stem Cells (drug effects)
• Humans
• Interleukin-11 (pharmacology)
• Interleukin-3 (pharmacology)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, drug therapy)
• Phenanthrolines (pharmacology)
• Stem Cell Factor (pharmacology)
• Tumor Stem Cell Assay