Lamy T, Drenou B, Fardel O, Amiot L, Grulois I, Le Prise P Y, Loughran T P, Fauchet R
Department of Hematology-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
Br J Haematol. 1998 Mar;100(3):509-15. doi: 10.1046/j.1365-2141.1998.00606.x.
Multi-drug resistance (MDR) phenotype contributes to the ineffectiveness of chemotherapy. P-glycoprotein (PgP) and lung resistance protein (LRP) are proteins implicated in chemoresistance. We analysed the expression of PgP and LRP respectively in 17 and 15 cases of lymphoproliferative disease of granular lymphocytes (LDGL) including 10 cases of clonal large granular lymphocytic (LGL) leukaemia, six cases of oligoclonal (n = 5) and polyclonal (n = 1) CD3+ lymphoproliferation and one case of CD3- NK lymphocytosis. Functional PgP activity, as determined by Rh123 dye efflux assay, was found in all the patients. The mean percentage of effluxing cells was 47 +/- 22%, compared to 35 +/- 8% on normal lymphocytes (P<0.04). The efflux was blocked in the presence of verapamil, a PgP revertant agent. A high proportion of CD57+ cells (66 +/- 10%) from these patients expelled Rh123. Functional PgP activity was associated with expression of MDR1 mRNA. By using immunocytochemistry, LRP expression was detected in 11/15 patients (73%). 7/10 LGL leukaemia patients presented a LRP+/Efflux+ phenotype and 5/7 had LRP+/Efflux+/MDR1 mRNA+ phenotype. These findings suggest that the PgP+/LRP+ phenotype is frequently observed in LDGL. Its clinical relevance in aggressive cases remains to be determined.
多药耐药（MDR）表型导致化疗无效。P-糖蛋白（PgP）和肺耐药蛋白（LRP）是与化疗耐药相关的蛋白。我们分别分析了17例颗粒淋巴细胞增殖性疾病（LDGL）和15例中的PgP和LRP表达，其中包括10例克隆性大颗粒淋巴细胞（LGL）白血病、6例寡克隆（n = 5）和多克隆（n = 1）CD3 +淋巴细胞增殖以及1例CD3 - NK淋巴细胞增多症。通过Rh123染料外排试验测定，发现所有患者均有功能性PgP活性。外排细胞的平均百分比为47±22%，而正常淋巴细胞为35±8%（P<0.04）。在PgP逆转剂维拉帕米存在的情况下，外排被阻断。这些患者中高比例的CD57 +细胞（66±10%）排出Rh123。功能性PgP活性与MDR1 mRNA的表达相关。通过免疫细胞化学方法，在11/15例患者（73%）中检测到LRP表达。7/10例LGL白血病患者呈现LRP + /外排 +表型，5/7例具有LRP + /外排 + /MDR1 mRNA +表型。这些发现表明，在LDGL中经常观察到PgP + /LRP +表型。其在侵袭性病例中的临床相关性仍有待确定。
