ISSN:
0021-9541
Keywords:
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Medicine
Notes:
We studied the effect of transforming growth factor-beta 1(TGF-β 1) on colony formation of leukemic blast progenitors from ten acute myeloblastic leukemia (AML) patients stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), or interleukin-1β (IL-1β). These CSFs and interleukins by themselves stimulated the proliferation of leukemic blast progenitors without adding TGF-β 1. G-CSF, GM-CSF, and IL-3 stimulated blast colony formation in nine patients, IL-6 stimulated it in five, and IL-1β stimulated in four. TGF-β 1 significantly reduced blast colony formation stimulated by G-CSF, GM-CSF, or IL-6 in all patients. In contrast, TGF-β 1 enhanced the stimulatory effect of IL-3 on blast progenitors from three cases, while in the other seven patients TGF-β 1 reduced blast colony formation in the presence of IL-3. To study the mechanism by which TGF-β 1 enhanced the stimulatory effect of IL-3 on blast progenitors, we carried out the following experiments in the three patients in which it occurred. First, the media conditioned by leukemic cells in the presence of TGF-β 1 stimulated the growth of leukemic blast progenitors, but such effect was completely abolished by anti-IL-1 β antibody. Second, the addition of IL-1 β in the culture significantly enhanced the growth of blast progenitors stimulated with IL-3. Third, leukemic cells of the two patients studied were revealed to secrete IL-1 β and tumor necrosis factor-α (TNF-α) constitutively; the production by leukemic cells of IL-1 β and TNF-α was significantly promoted by TGF-β 1. Furthermore, the growth enhancing effect of TGF-β 1 in the presence of IL-3 was fully neutralized by anti-IL-1 β antibody. These findings suggest that TGF-β 1 stimulated the growth of blast progenitors through the production and secretion of IL-1 β by leukemic cells.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcp.1041480310
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