Enhancement by transforming growth factor-β 1 (TGF-β 1) of the proliferation of leukemic blast progenitors stimulated with IL-3

✍ Scribed by Toshiya Suzuki; Masami Bessho; Kunitake Hirashima; Shuji Tohda; Kaoru Nagata; Tomohiro Morio; Yasufumi Imai; Nobuo Nara

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 764 KB
• Volume: 148
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041480310

✦ Synopsis

Abstract

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.