Terui T, Niitsu Y, Mahara K, Fujisaki Y, Urushizaki Y, Mogi Y, Kohgo Y, Watanabe N, Ogura M, Saito H
Department of Internal Medicine (Section 4), Sapporo Medical College, Japan.
Blood. 1990 Apr 1;75(7):1540-8.
Acute myelofibrosis is often associated with acute megakaryoblastic leukemia (AMKBL). Although the exact mechanism for the progression of myelofibrosis in AMKBL is unclear, certain humoral factors from megakaryoblastic cells, the precursors of platelets, may be involved in the enhancement of collagen synthesis by bone marrow fibroblasts. The present study, therefore, is an investigation of the possible pathogenic role of transforming growth factor-beta (TGF-beta), known to be a very potent collagen-stimulating factor found in platelets in the myelofibrosis of AMKBL. The results obtained were as follows: (1) Conditioned media from peripheral megakaryoblasts taken from an AMKBL patient and from established megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on collagen synthesis in bone marrow fibroblasts than conditioned media from other leukemic cell types. (2) Based on an assessment of soft agar colony formation, there was greater TGF-beta activity in media that had been conditioned from megakaryoblasts than in media from other leukemic cell types. (3) When compared with other leukemic-cell types, megakaryoblasts showed substantially greater expression of TGF-beta mRNA that was hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of the anti-TGF-beta antibody inhibited the stimulatory effects of the megakaryoblast conditioned medium on collagen synthesis in bone marrow fibroblasts. These results clearly suggest that megakaryoblasts produce and secrete an active form of TGF-beta and stimulate collagen synthesis in bone marrow fibroblasts in a paracrine manner.
急性骨髓纤维化常与急性巨核细胞白血病（AMKBL）相关。尽管AMKBL中骨髓纤维化进展的确切机制尚不清楚，但血小板前体巨核细胞产生的某些体液因子可能参与增强骨髓成纤维细胞的胶原合成。因此，本研究旨在探讨转化生长因子-β（TGF-β）在AMKBL骨髓纤维化中可能的致病作用，已知TGF-β是血小板中一种非常有效的胶原刺激因子。获得的结果如下：（1）来自一名AMKBL患者外周血巨核母细胞和已建立的巨核母细胞系（MEG-01）的条件培养基对骨髓成纤维细胞胶原合成的刺激作用远大于其他白血病细胞类型的条件培养基。（2）基于软琼脂集落形成评估，巨核母细胞条件培养基中的TGF-β活性高于其他白血病细胞类型的培养基。（3）与其他白血病细胞类型相比，巨核母细胞显示出在2.5 kb处与TGF-β cDNA探针杂交的TGF-β mRNA表达显著更高，并且用抗TGF-β抗体在13 Kd处检测到TGF-β多肽。（4）抗TGF-β抗体的添加抑制了巨核母细胞条件培养基对骨髓成纤维细胞胶原合成的刺激作用。这些结果清楚地表明，巨核母细胞产生并分泌活性形式的TGF-β，并以旁分泌方式刺激骨髓成纤维细胞的胶原合成。
