Sagayadan G E, Wiernik P H, Sun N, Ahearn G, Thompson D, Hallam S J, Hu X P, Dutcher J P, Gallagher R E
Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY 10467.
Leuk Res. 1994 Oct;18(10):741-8. doi: 10.1016/0145-2126(94)90055-8.
Granulocyte-macrophage colony forming units (CFU-GM) from patients with advanced stage chronic myelogenous leukemia (CML), i.e. in blastic crisis (BC) or accelerated phase (AP), were inhibited by all-trans-retinoic acid (tRA) approximately 1000-fold more potently than those from chronic phase (CP) CML patients (median IC50 = 10(-9) M tRA for six CML-AP/BC cases vs > 10(-6) M tRA for seven CML-CP cases). A similar activity pattern was observed for the stereoisomer 13-cis-RA (cRA). There was no apparent correlation of CFU-GM retinoid sensitivity with cloning efficiency or other colony characteristics. Interferon alpha-2a (INF alpha) alone strongly inhibited CFU-GM growth in all four CML-AP/BC cases (IC50 < or = 250 IU/ml) and three out of seven CML-CP cases (IC50 < or = 500 IU/ml), but there was little or no interactive effect between various concentrations of tRA and INF alpha (50 IU/ml) on CFU-GM from either CML-AP/BC or CML-CP cases. These results suggest that CML-AP/BC CFU-GM have some intrinsic molecular alteration(s) which markedly enhances their responsiveness to tRA and cRA, which may be clinically exploitable.
来自晚期慢性粒细胞白血病（CML）患者，即处于急变期（BC）或加速期（AP）的粒-巨噬细胞集落形成单位（CFU-GM），被全反式维甲酸（tRA）抑制的程度比慢性期（CP）CML患者的CFU-GM强约1000倍（6例CML-AP/BC病例的tRA中位IC50 = 10^(-9) M，而7例CML-CP病例的tRA > 10^(-6) M）。对于立体异构体13-顺式维甲酸（cRA）也观察到类似的活性模式。CFU-GM对维甲酸的敏感性与克隆效率或其他集落特征之间没有明显相关性。单独使用干扰素α-2a（INFα）能强烈抑制所有4例CML-AP/BC病例（IC50 ≤ 250 IU/ml）和7例CML-CP病例中的3例（IC50 ≤ 500 IU/ml）的CFU-GM生长，但不同浓度的tRA和INFα（50 IU/ml）对CML-AP/BC或CML-CP病例的CFU-GM几乎没有交互作用。这些结果表明，CML-AP/BC的CFU-GM存在一些内在分子改变，显著增强了它们对tRA和cRA的反应性，这可能具有临床应用价值。
