Curtis D J, Metcalf D, Alexander B, Begley C G
The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Exp Hematol. 2000 Jan;28(1):36-45. doi: 10.1016/s0301-472x(99)00123-x.
Human acute myeloid leukemia (AML) cells can proliferate in vitro in the absence of added growth factors when cultured at high cell density. Autocrine growth factor production is a postulated mechanism of autonomous growth. We sought to examine this using murine AML cells.
We have utilized a Moloney murine leukemia virus (M-MuLV) model of AML to investigate the nature of autonomous in vitro growth of myeloid leukemic cells.
Like human AML, M-MuLV-induced myeloid leukemic cells displayed autonomous growth in unstimulated high cell density cultures. However, replating of individual, primary, growth factor autonomous colonies of leukemic cells demonstrated the presence of clonogenic cells capable of autonomous growth when cultured at low cell density. In addition, there was heterogeneity in the progeny of these cells: both factor-dependent leukemic cells and cells autonomous of exogenous factor were observed.
We propose that clonogenic cells capable of autonomous growth at low cell density represent leukemic progenitors while the majority of leukemic cells derived from these "autonomous" leukemic cells are factor-dependent.
人急性髓系白血病(AML)细胞在高细胞密度培养时,无需添加生长因子即可在体外增殖。自分泌生长因子的产生是自主生长的一种假定机制。我们试图用小鼠AML细胞对此进行研究。
我们利用一种AML的莫洛尼鼠白血病病毒(M-MuLV)模型来研究髓系白血病细胞体外自主生长的性质。
与人类AML一样,M-MuLV诱导的髓系白血病细胞在未刺激的高细胞密度培养中表现出自主生长。然而,对白血病细胞的单个、原代、生长因子自主克隆进行再接种,结果表明存在能够在低细胞密度培养时自主生长的克隆形成细胞。此外,这些细胞的子代存在异质性:观察到既有因子依赖性白血病细胞,也有对外源因子自主的细胞。
我们提出,能够在低细胞密度时自主生长的克隆形成细胞代表白血病祖细胞,而源自这些“自主”白血病细胞的大多数白血病细胞是因子依赖性的。