Cornic M, Guidez F, Delva L, Agadir A, Degos L, Chomienne C
Laboratoire de biologie cellulaire hématopoïétique, hôpital Saint-Louis, Paris, France.
Bull Cancer. 1992;79(7):697-704.
Vitamin A (retinol) and retinoic acid, its natural derivative, play an important role in the growth, differentiation and development of known normal tissues. Retinoids have recently become of interest to research in areas as diverse as dermatology, embryonal development and cancer research. Retinol is the major retinoid transported in the blood and tissues by its specific carrier retinol binding protein (RBP). The normal level of retinol in plasma is regulated very precisely by retinol homeostasis. RBP-retinol circulation supplies target cells, which then activate retinol into retinoic acid (RA) if they possess the NAD-dependent enzymatic oxidation system. RA, which is one of the most active metabolites of retinol, is also present in low concentration in the blood and the RA rate formation varies from tissues depending on specific need of the cell. The cellular transport and biological activity of retinoids may be mediated by their specific cytoplasmic binding proteins cellular retinol binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) which may function as shuttles targetting RA to nucleosol fraction and/or as regulator of cellular concentration of RA. The nuclear proteins RARs (retinoic acid receptors), which are members of the nuclear receptor superfamily are likely to be the final transducers of the RA signal at the gene expression. All-trans retinoic acid (ATRA) is able to specifically differentiate the malignant cells from leukemic patients with APL in short-term culture. For this reason, APL patients were successfully treated with ATRA (Chinese and French results). Acute promyelocytic leukemia M3 (French-American-British FAB classification) is a rare disease (10% of AML), characterized by a reciprocal chromosome 15-17 translocation. It has been shown that the chromosome 17 breakpoint of the translocation is localized within the RAR alpha gene. Due to the t(15;17) RAR alpha gene translocated to a gene PML on chromosome 15 resulting in synthesis of PML/RAR alpha fusion messenger RNA. Detection of PML/RAR alpha transcript is now a molecular marker of the disease. The abnormal PML/RAR alpha protein exhibits altered transcription activation properties when compared with RAR alpha. Clinical trials have demonstrated that ATRA is extremely efficient in inducing complete remission in APL patients. The morphologic finding of maturing elements in the bone marrow and peripheral blood during retinoic acid treatment indicates that the remission is obtained without hypoplasia and suggests that a differentiating mechanism is involved.(ABSTRACT TRUNCATED AT 400 WORDS)
维生素A（视黄醇）及其天然衍生物视黄酸在已知正常组织的生长、分化和发育中发挥着重要作用。类视黄醇最近在皮肤病学、胚胎发育和癌症研究等不同领域的研究中受到关注。视黄醇是通过其特定载体视黄醇结合蛋白（RBP）在血液和组织中运输的主要类视黄醇。血浆中视黄醇的正常水平由视黄醇稳态非常精确地调节。RBP-视黄醇循环为靶细胞提供物质，如果靶细胞拥有NAD依赖性酶促氧化系统，它们会将视黄醇激活为视黄酸（RA）。RA是视黄醇最活跃的代谢产物之一，在血液中也以低浓度存在，并且RA的生成速率因组织而异，取决于细胞的特定需求。类视黄醇的细胞运输和生物活性可能由其特定的细胞质结合蛋白细胞视黄醇结合蛋白（CRBP）和细胞视黄酸结合蛋白（CRABP）介导，它们可能充当将RA靶向核溶胶部分的穿梭载体和/或作为RA细胞浓度的调节剂。核蛋白视黄酸受体（RARs）是核受体超家族的成员，可能是基因表达时RA信号的最终转导者。全反式视黄酸（ATRA）能够在短期培养中将急性早幼粒细胞白血病（APL）患者的恶性细胞特异性分化。因此，ATRA成功治疗了APL患者（中国和法国的结果）。急性早幼粒细胞白血病M3（法美英FAB分类）是一种罕见疾病（占急性髓系白血病的10%），其特征是15号和17号染色体相互易位。已经表明，该易位的17号染色体断点位于RARα基因内。由于t(15;17)，RARα基因易位到15号染色体上的一个基因PML，导致PML/RARα融合信使核糖核酸的合成。检测PML/RARα转录本现在是该疾病的一个分子标志物。与RARα相比，异常的PML/RARα蛋白表现出改变的转录激活特性。临床试验表明，ATRA在诱导APL患者完全缓解方面极其有效。维甲酸治疗期间骨髓和外周血中成熟细胞成分的形态学发现表明，缓解是在没有发育不全的情况下获得的，这表明涉及一种分化机制。（摘要截选至400字）
