Constitutive and induced expression of growth factors in normal and chronic phase chronic myelogenous leukemia Ph1 bone marrow stroma

Cancer Res. 1990 Sep 15;50(18):5801-5.

Abstract

Study of growth factor RNA levels in the stromal cells derived from the adherent layer of long-term bone marrow culture demonstrated constitutive expression of transforming growth factor beta 1 (TGF-beta 1) and macrophage colony-stimulating factor. These cells did not express granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interleukin (IL) 1 alpha, IL-1 beta, IL-3, and IL-6. However, granulocyte colony-stimulating factor expression could be induced by recombinant human IL-1 beta; while IL-6 could be induced by both IL-1 beta and tumor necrosis factor-alpha. No differences could be detected between adherent layers established from normal and benign phase Ph1 chronic myelogenous leukemia bone marrow. The uninduced expression of TGF-beta 1, a potent hematopoietic cell growth inhibitor, suggests that stromal cells play an inherent role in regulating the proliferation of adjacent bone marrow hematopoietic progenitor cells. However, a defect in stromal TGF-beta 1 production cannot account for the profoundly expanded myeloid compartment in chronic phase chronic myelogenous leukemia. In contrast to the constitutive expression of TGF-beta 1 and macrophage colony-stimulating factor, hematopoietic growth factors are only expressed following a proper stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Factors / genetics
  • Biological Factors / pharmacology
  • Bone Marrow / metabolism*
  • Cells, Cultured
  • Colony-Stimulating Factors / genetics*
  • Cytokines
  • Gene Expression*
  • Gene Rearrangement
  • Humans
  • Interleukins / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Macrophage Colony-Stimulating Factor
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcr
  • RNA, Messenger / analysis
  • Transforming Growth Factors / genetics*

Substances

  • Biological Factors
  • Colony-Stimulating Factors
  • Cytokines
  • Interleukins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transforming Growth Factors
  • Macrophage Colony-Stimulating Factor
  • Protein-Tyrosine Kinases
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr