Retinoids. Structure-function relationship in normal and leukemic hematopoiesis in vitro.
Retinoids. Structure-function relationship in normal and leukemic hematopoiesis in vitro.
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类维生素A。
DOI：
10.1172/jci112565
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Koeffler,HP
中科院分区：
文献类型：
--
作者：
Tobler,A;Dawson,MI;Koeffler,HP
类维生素A的研究，以确定什么样的骨骼成分是重要的正常和白血病的人骨髓克隆增殖和分化的调制在体外，并阐明类维生素A调节造血细胞增殖的机制。具有衍生化末端羧基的类维生素A活性显著低于全反式维甲酸，并且在维甲酸的环己烯基环上添加两个甲基或用1，1，3，3 -5-茚满基环系统取代其β-环香叶基亚基的类维生素A活性显著高于全反式维甲酸。其中5种维甲酸对HL-60和KG-1人白血病细胞系的克隆生长有强烈的抑制作用（在3 × 10（-10）-1 × 10（-8）M范围内抑制50%），并明显刺激正常人骨髓集落形成（在3 × 10（-9）-3 × 10（-8）M范围内对粒细胞-巨噬细胞集落形成细胞[GM-CFC]刺激150%）。进一步的研究表明：类维生素A的共同结构要求在调节正常和白血病造血中是重要的。类维生素A能够抑制白血病细胞的增殖，而不诱导肿瘤细胞的分化。对正常人GM-CFC的研究表明，类维生素A本身不是集落刺激因子（CSF），也不是通过刺激辅助细胞产生CSF而起作用，而是需要较早的祖细胞成为GM-CFC或增强GM-CFC对CSF作用的敏感性。
Retinoids were studied both to identify what skeletal components are important in the modulation of normal and leukemic human myeloid clonal proliferation and differentiation in vitro and to elucidate the mechanism by which retinoids modulate proliferation of hematopoietic cells. Retinoids with a derivatized terminal carboxyl group were significantly less active than all-trans-retinoic acid, and those with the addition of two methyl groups to the cyclohexenyl ring of retinoic acid or substitution of its beta-cyclogeranylidene group with a 1,1,3,3-5-indanyl ring system were markedly more active than all-trans-retinoic acid. Five of the retinoids strongly inhibited clonal growth of the HL-60 and KG-1 human leukemic cell lines (50% inhibition in the range of 3 X 10(-10)-1 X 10(-8) M) and markedly stimulated normal human myeloid colony formation (granulocyte-macrophage colony-forming cells [GM-CFC] 150% stimulation in the range of 3 X 10(-9)-3 X 10(-8) M). Further studies suggested that: Common structural requirements of the retinoids were important in the modulation of both normal and leukemic hematopoiesis. The retinoids were able to inhibit leukemic proliferation without induction of differentiation of the neoplastic cells. Studies on normal human GM-CFC suggested that the retinoids did not act by themselves as a colony-stimulating factor (CSF), or by stimulating accessory cells to produce CSF, but either required earlier progenitor cells to become GM-CFC or enhanced the sensitivity of GM-CFC to the action of CSF.