De Stefano V, Teofili L, Sica S, Mastrangelo S, Di Mario A, Rutella S, Salutari P, Rumi C, d'Onofrio G, Leone G
Istituto di Semeiotica Medica, Università Cattolica, Rome, Italy.
Blood. 1995 Nov 1;86(9):3535-41.
The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u-PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.
急性早幼粒细胞白血病（APL）凝血障碍及其通过全反式维甲酸（ATRA）给药逆转的潜在机制已得到研究。将9例APL患者的骨髓早幼粒细胞在有或无1μmol/L ATRA的情况下进行培养。培养的细胞（第0、3、6和9天）经洗涤后重悬于磷酸盐缓冲液中，通过冻融裂解，然后检测促凝活性（PCA）、弹性蛋白酶活性、组织因子（TF）抗原、组织型纤溶酶原激活剂（t-PA）抗原和尿激酶型纤溶酶原激活剂（u-PA）抗原。PCA通过复钙试验测定。弹性蛋白酶通过酰胺分解试验（S-2484）测量。TF、t-PA和u-PA抗原通过酶联免疫吸附试验（ELISA）测量。与对照多形核细胞相比，从患者分离出的恶性早幼粒细胞的PCA和TF水平升高，而弹性蛋白酶、t-PA和u-PA水平较低；患者原始细胞PCA水平与纤维蛋白原血症程度显著相关。在该系统中，原始细胞PCA依赖于组织因子，且与TF抗原值显著相关。在无ATRA的培养物中，PCA、TF和u-PA逐渐增加，而弹性蛋白酶和t-PA水平基本保持不变。在有ATRA的情况下，所有参数（u-PA除外）在培养期间均下降。因此，提示早幼粒细胞原始细胞PCA在M3相关凝血障碍的发病机制中起主要作用；ATRA对凝血障碍的作用似乎主要通过PCA的下调介导。
