Michieli M, Damiani D, Ermacora A, Raspadori D, Michelutti A, Grimaz S, Fanin R, Russo D, Lauria F, Masolini P, Baccarani M
Department of Bone Marrow Transplantation, University and General Hospital, Udine, Italy.
Br J Haematol. 1997 Feb;96(2):356-65. doi: 10.1046/j.1365-2141.1997.d01-2020.x.
P-glycoprotein (PGP) lung resistance protein (LRP) and multidrug resistance associated protein (MRP) expressions and function were evaluated by flow cytometry in 65 leukaemic patients (38 acute non-lymphocytic leukaemias, eight acute lymphocytic leukaemias, 19 Ph-positive chronic myeloid leukaemias in blastic phase). By using the MRK-16, the LRP-56 and the MRPm6 MoAbs, 34% of the cases did not over-express any proteins (-); 24.5% over-expressed (+) only PGP, 11% only LRP, 1.5% only MRP, 24.5% both PGP and LRP, and 4.5% both PGP and MRP. The mean intracellular daunorubicin accumulation (IDA) and rhodamine 123 (Rh123) retention in the presence or absence of the reversal agent SDZ PSC 833 (PSC) of the PGP-/LRP-/MRP- cases were comparable to the ones observed in normal leucocytes. With respect to the non-over-expressing cases, the PGP-/LRP+/MRP- cases showed only an impaired IDA (mean 204 +/- 29; P < 0.001). The PGP+/ LRP+/MRP- cases had a defect both in IDA (mean 166 +/- 47, P < 0.001) and Rh123 retention (mean 0.42 +/- 0.14: P < 0.001), which were both corrected by PSC. All the PGP+/LRP+/MRP- cases had a defect in IDA (mean daunorubicin (DNR) accumulation 192 +/- 44; P < 0.001). However, only in 8/16 of them an evident defect in Rh123 retention was found. In conclusion, both PGP and LRP over-expression were common in leukaemia. An impaired IDA was found in all cases over-expressing PGP, LRP or both. The study of Rh123 retention could give incorrect information about the blast cells' ability to accumulate cytotoxic drugs in patients over-expressing both PGP and LRP.
采用流式细胞术对65例白血病患者（38例急性非淋巴细胞白血病、8例急性淋巴细胞白血病、19例急变期Ph阳性慢性髓性白血病）的P-糖蛋白（PGP）、肺耐药蛋白（LRP）和多药耐药相关蛋白（MRP）的表达及功能进行评估。使用MRK-16、LRP-56和MRPm6单克隆抗体，34%的病例未过度表达任何蛋白（-）；24.5%仅过度表达（+）PGP，11%仅过度表达LRP，1.5%仅过度表达MRP，24.5%同时过度表达PGP和LRP，4.5%同时过度表达PGP和MRP。PGP-/LRP-/MRP-病例在存在或不存在PGP逆转剂SDZ PSC 833（PSC）的情况下，平均细胞内柔红霉素蓄积（IDA）和罗丹明123（Rh123）潴留与正常白细胞中观察到的情况相当。与未过度表达的病例相比，PGP-/LRP+/MRP-病例仅表现出IDA受损（平均值204±29；P<0.001）。PGP+/LRP+/MRP-病例在IDA（平均值166±47，P<0.001）和Rh123潴留（平均值0.42±0.14：P<0.001）方面均有缺陷，二者均被PSC纠正。所有PGP+/LRP+/MRP-病例在IDA方面均有缺陷（平均柔红霉素（DNR）蓄积192±44；P<0.001）。然而，其中只有8/16的病例在Rh123潴留方面存在明显缺陷。总之，PGP和LRP过度表达在白血病中均很常见。在所有过度表达PGP、LRP或二者的病例中均发现IDA受损。对于同时过度表达PGP和LRP的患者，Rh123潴留研究可能会提供关于原始细胞蓄积细胞毒性药物能力的错误信息。
