Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias
Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias
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DOI：
10.1158/1078-0432.ccr-04-0795
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发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Legrand, O
中科院分区：
文献类型：
--
作者：
Benderra, Z;Faussat, AM;Legrand, O
目的：最近发现了一种新的ABC蛋白--乳腺癌耐药蛋白（BCRP）.但其预后在急性髓细胞白血病（AML）中尚不清楚。此外，在所有阿雷胞汀治疗期间，接受相同蒽环类药物（柔红霉素、伊达比星或米托蒽醌）均匀治疗的患者的P-糖蛋白（Pgp）和BCRP的预后尚不清楚。因此，我们已经评估了耐药表型之间的关系，在体外蒽敏感性，和治疗outcome.Experimental设计的关系：我们分析了149 AML治疗根据欧洲组织的研究和治疗癌症组的协议。分析BCRP和Pgp在全人群中及按不同嵌入剂的预后价值。BCRP是实现完全缓解的预后因素（阳性患者为43%，阴性患者为69%，P = 0.005），4年无病生存率（12%对33%，P = 0.03），和4年总生存率（19%对38%，P = 0.003）。当BCRP表达和Pgp功能分为+/+、+/-或-/+和-/-三组时，完全缓解率分别为45%、66%和90%。4年无瘤生存率分别为8%、26%和40%（P = 0.01），4年总生存率分别为16%、37%和48%（P = 0.001）。Pgp功能是柔红霉素和伊达比星治疗患者的预后因素，而不是米托蒽醌。与此相反，BCRP的表达是一个预后因素，柔红霉素和米托蒽醌治疗的患者，但不是由idareclamp.Conclusions：BCRP将牵连在化疗耐药的AML。但同时表达BCRP和Pgp的患者预后最差。
Purpose: Recently, a new ABC protein, breast cancer resistance protein (BCRP), was described. But its prognosis is not known in acute myeloid leukemia (AML). In addition, the prognosis of P-glycoprotein (Pgp) and BCRP in patients treated homogeneously by the same anthracycline (daunorubicin, idarubicin, or mitoxantrone) during all of the treatment with aracytine is not known. Therefore, we have evaluated the relationship between drug resistance phenotype, in vitro anthracene sensitivity, and the relation to treatment outcome.Experimental Design: We have analyzed 149 AML treated according to protocol of the European Organization for Research and Treatment of Cancer group. The prognostic value of BCRP and Pgp were analyzed in the whole population and according to intercalating agent.Results: BCRP was a prognostic factor, for achievement of complete remission (43% in positive patients and 69% in negative patients, P = 0.005), the 4-year disease-free survival (12% versus 33%, P = 0.03), and the 4-year overall survival (19% versus 38%, P = 0.003). When BCRP expression and Pgp function were categorized in three groups, +/+, +/- or -/+, and -/-, the achievement of complete remission was 45%, 66%, and 90% (P = 0.0003), the 4-year disease-free survival was 8%, 26%, and 40% (P = 0.01), and the 4-year overall survival was 16%, 37%, and 48% (P = 0.001), respectively. Pgp function was a prognostic factor in patients treated by daunorubicin and idarubicin but not by mitoxantrone. In contrast, BCRP expression was a prognostic factor in patients treated by daunorubicin and mitoxantrone but not by idarubicin.Conclusions: BCRP would be implicated in the resistance to chemotherapies in AML. But these are the patients expressing both BCRP and Pgp who have the poorest prognosis.