Preudhomme C, Lepelley P, Vachee A, Soenen V, Quesnel B, Cosson A, Fenaux P
Laboratoire d'Hématologie, C.H.U., Lille, France.
Leukemia. 1993 Nov;7(11):1888-90.
P glycoprotein, the product of multidrug resistance (mdr1) gene, is frequently expressed in advanced myelodysplastic syndromes (MDS) with an excess of bone marrow blasts and could explain their frequent resistance to chemotherapy. P53 gene mutations are also found in 10 to 15% of advanced MDS. Because it has recently been suggested that normal p53 suppressed, but that mutated p53 activated, the mdr1 gene promoter, we tried to correlate p53 mutations and P glycoprotein expression in 34 patients with MDS and an excess of bone marrow blasts (> 5%). P glycoprotein expression was assessed by immunocytochemistry using JSB1 monoclonal antibody and was found positive in 13 out of the 34 patients. p53 mutations were detected both by immunocytochemistry using three different monoclonal antibodies and by single stranded conformation polymorphism (SSCP) analysis of exons 5 to 8 of the P53 gene. Both methods detected a point mutation in 5 out of the 34 patients. Only one out of the 5 patients with a p53 mutation expressed P glycoprotein, as compared to 12 out of the 29 patients without p53 mutations. This suggested the mutant and normal p53 are not major determinants of the regulation of mdr1 expression in vivo, at least in MDS.
P糖蛋白是多药耐药（mdr1）基因的产物，在骨髓母细胞增多的晚期骨髓增生异常综合征（MDS）中经常表达，这可能解释了它们对化疗的频繁耐药性。在10%至15%的晚期MDS中也发现了P53基因突变。由于最近有人提出正常的p53会抑制mdr1基因启动子，但突变的p53会激活它，我们试图在34例骨髓母细胞增多（>5%）的MDS患者中，将P53基因突变与P糖蛋白表达进行关联。使用JSB1单克隆抗体通过免疫细胞化学评估P糖蛋白表达，在34例患者中有13例呈阳性。通过使用三种不同单克隆抗体的免疫细胞化学以及对P53基因第5至8外显子的单链构象多态性（SSCP）分析来检测p53突变。两种方法在34例患者中均检测到5例存在点突变。在5例有p53突变的患者中只有1例表达P糖蛋白，而在29例无p53突变的患者中有12例表达。这表明突变型和正常型p53至少在MDS中并非体内mdr1表达调控的主要决定因素。
