Constitutive and induced expression of growth factors in normal and chronic phase chronic myelogenous leukemia Ph1 bone marrow stroma.
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.
Wetzler
M
M
Department of Clinical Immunology and Biological Therapy, M.D. Anderson Cancer Center, Houston, Texas 77030.
Kurzrock
R
R
Taylor
K
K
Spitzer
G
G
Kantarjian
H
H
Baiocchi
G
G
Ku
S
S
Gutterman
J U
JU
Talpaz
M
M
D001685:Biological Factors / Q000235:genetics / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000235:genetics*; D016207:Cytokines; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D007378:Interleukins / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051562:Proto-Oncogene Proteins c-bcr; D012333:RNA, Messenger / Q000032:analysis; D015291:Transforming Growth Factors / Q000235:genetics*
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr