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

Leuk Res. 1996 Sep;20(9):751-9. doi: 10.1016/0145-2126(96)00039-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Phenanthrolines / pharmacology*
  • Stem Cell Factor / pharmacology
  • Tumor Stem Cell Assay

Substances

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