Nara N
Laboratory Medicine, Tokyo Medical and Dental University, Japan.
Leuk Lymphoma. 1993 Jun;10(3):201-7. doi: 10.3109/10428199309145884.
The effects of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) on the growth of leukemic blast progenitors in 6 acute myeloblastic leukemia (AML) patients, 1 chronic myelocytic leukemia (CML) patient in blast crisis and a granulocyte colony-stimulating factor-(G-CSF-) dependent OCI/AML1a cell line established from an AML patient, were studied. Cells of fresh blood samples and the OCI-AML1a cell line were cultured in methylcellulose media and suspension culture in the presence of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) supplemented as a growth stimulatory factor. Both cytokines suppressed the primary and secondary colony formation in methylcellulose culture of leukemic blast progenitors. The recovery of clonogenic cells in suspension culture was also suppressed by IFN-gamma and TNF-alpha. The primary colony formation in methylcellulose reflects the terminal divisions of leukemic blast progenitors, while the secondary colony formation in methylcellulose and the clonogenic cell recovery in suspension have been considered to reflect their self-renewal capacity. Therefore, IFN-gamma and TNF-alpha are considered to be effective in suppressing not only the terminal divisions but also self-renewal of leukemic blast progenitors. When both cytokines were added simultaneously to cultures, the suppressive effect of each cytokine was enhanced. The results may suggest the effectiveness of IFN-gamma and TNF-alpha in the treatment of leukemia.
研究了干扰素-γ（IFN-γ）和/或肿瘤坏死因子-α（TNF-α）对6例急性髓细胞白血病（AML）患者、1例处于急变期的慢性粒细胞白血病（CML）患者以及从1例AML患者建立的依赖粒细胞集落刺激因子（G-CSF）的OCI/AML1a细胞系中白血病原始祖细胞生长的影响。新鲜血液样本的细胞和OCI-AML1a细胞系在甲基纤维素培养基中培养，并在添加G-CSF、粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-3（IL-3）作为生长刺激因子的情况下进行悬浮培养。两种细胞因子均抑制白血病原始祖细胞在甲基纤维素培养中的一级和二级集落形成。悬浮培养中克隆形成细胞的恢复也受到IFN-γ和TNF-α的抑制。甲基纤维素中的一级集落形成反映白血病原始祖细胞的终末分裂，而甲基纤维素中的二级集落形成和悬浮培养中克隆形成细胞的恢复被认为反映其自我更新能力。因此，IFN-γ和TNF-α被认为不仅能有效抑制白血病原始祖细胞的终末分裂，还能抑制其自我更新。当将两种细胞因子同时添加到培养物中时，每种细胞因子的抑制作用都会增强。这些结果可能提示IFN-γ和TNF-α在白血病治疗中的有效性。
