Bosanquet A G, Bell P B, Burlton A R, Amos T A
Bath Cancer Research Unit, School of Postgraduate Medicine, University of Bath, Royal United Hospital, UK.
Leuk Lymphoma. 1996 Dec;24(1-2):141-7. doi: 10.3109/10428199609045722.
We compared bcl-2 with P-glycoprotein expression (C494 and JSB1), and both with ex vivo chemosensitivity by Differential Staining Cytotoxicity (DiSC) assay (25 cytotoxic drugs), in 76 fresh haematological specimens, including 51 chronic lymphocytic leukaemias (CLL). Strong correlations were seen between bcl-2 and Pgp expression in both CLL (r = 0.5; p < 0.001) and AML (r = 0.9; p < 0.001) although bcl-2 expression was only raised in Pgp positive cells. However, there was no correlation between high or low marker levels and either ex vivo drug sensitivity (-0.30 < r < 0.37; p all > 0.1) or patient survival (chi 2 < or = 0.1; p > 0.7). One B-CLL, one PLL and one hairy cell leukaemia were negative for both bcl-2 and Pgp, whilst 3 T-cell specimens were bcl-2 negative but strongly positive for Pgp. These results suggest that the expression of Pgp and bcl-2 may be interlinked and related to immunophenotype and that clinical sensitivity to MDR-inducing and/or apoptosis-inducing drugs is best determined by ex vivo chemosensitivity testing rather than measurement of Pgp or bcl-2 expression.
我们在76份新鲜血液学标本(包括51例慢性淋巴细胞白血病(CLL))中,比较了bcl-2与P-糖蛋白表达(C494和JSB1),并通过差异染色细胞毒性(DiSC)测定法(25种细胞毒性药物)将二者与体外化学敏感性进行了比较。在CLL(r = 0.5;p < 0.001)和AML(r = 0.9;p < 0.001)中,均观察到bcl-2与Pgp表达之间存在强相关性,尽管bcl-2表达仅在Pgp阳性细胞中升高。然而,标志物水平的高低与体外药物敏感性(-0.30 < r < 0.37;所有p > 0.1)或患者生存率(卡方值≤0.1;p > 0.7)均无相关性。1例B-CLL、1例PLL和1例毛细胞白血病的bcl-2和Pgp均为阴性,而3份T细胞标本bcl-2阴性但Pgp强阳性。这些结果表明,Pgp和bcl-2的表达可能相互关联且与免疫表型有关,对多药耐药诱导和/或凋亡诱导药物的临床敏感性最好通过体外化学敏感性测试来确定,而不是通过测量Pgp或bcl-2表达。