Lamy T, Drenou B, Grulois I, Fardel O, Jacquelinet C, Goasguen J, Dauriac C, Amiot L, Bernard M, Fauchet R
Service d'Hématologie Clinique, France.
Leukemia. 1995 Sep;9(9):1549-55.
We prospectively analyzed MDR functional activity by the Rh123 efflux assay in 84 de novo acute leukemias. Thirty of the 60 AML cases (50%) showed a positive dye efflux (in more than 10% of blast cells). In 19 cases, the dye efflux was superior to 30%. Twenty-four of the 30 efflux positive cases were CD34+ and could be studied in double staining. The mean percentage of effluxing CD34+ blast cells was 54%. There was a high correlation between CD34 expression and MDR activity (P < 10(-4)), MDR activity and PgP expression (P < 10(-6)). All the efflux negative samples were PgP negative. Nine efflux positive cases were PgP negative. Five of the 24 ALL were efflux positive. MDR activity did not correlate with FAB subtype (with the exception of AML3: 1/6 was efflux positive), age, white blood cell count or LDH level. Forty-seven AML patients were treated with conventional chemotherapy including cytarabine and an anthracycline. Thirty-one (66%) entered complete remission (CR). CR rate was statistically lower for efflux positive as compared to efflux negative patients, 46 vs 87% (P = 0.003), for PgP+ as compared to PgP- patients, 40 vs 78% (P = 0.01), for CD34+ as compared to CD34- patients, 45 vs 84% (P = 0.005). There was no correlation between P110 expression (32 AML cases studied) and FAB subtype, MDR status and clinical outcome. Two years survival was 20% for efflux positive patients as compared to 54% for efflux negative patients (P < 0.07), 15% for PgP+ vs 54% for PgP- patients (P < 0.04). The finding of efflux+/PgP- cases suggests the existence of other membrane efflux pumps. Rh123 efflux assay is straightforward in routine and could be included in MDR screening because of its potential interest in clinical outcome in AML.
我们采用Rh123外排试验对84例初发急性白血病患者的多药耐药（MDR）功能活性进行了前瞻性分析。60例急性髓系白血病（AML）患者中有30例（50%）显示染料外排阳性（超过10%的原始细胞）。19例患者的染料外排率超过30%。30例外排阳性病例中有24例为CD34+，可进行双重染色研究。外排的CD34+原始细胞的平均百分比为54%。CD34表达与MDR活性之间存在高度相关性（P < 10(-4)），MDR活性与P糖蛋白（PgP）表达之间也存在高度相关性（P < 10(-6)）。所有外排阴性样本的PgP均为阴性。9例外排阳性病例的PgP为阴性。30例急性淋巴细胞白血病（ALL）中有5例外排阳性。MDR活性与FAB亚型（AML3除外：1/6外排阳性）、年龄、白细胞计数或乳酸脱氢酶（LDH）水平均无相关性。47例AML患者接受了包括阿糖胞苷和蒽环类药物在内的传统化疗。31例（66%）达到完全缓解（CR）。外排阳性患者的CR率在统计学上低于外排阴性患者，分别为46%和87%（P = 0.003）；PgP阳性患者低于PgP阴性患者，分别为40%和78%（P = 0.01）；CD34+患者低于CD34-患者，分别为45%和84%（P = 0.005）。P110表达（研究了32例AML病例）与FAB亚型、MDR状态及临床结局之间无相关性。外排阳性患者的两年生存率为20%，外排阴性患者为54%（P < 0.07）；PgP阳性患者为15%，PgP阴性患者为54%（P < 0.04）。外排阳性/PgP阴性病例的发现提示存在其他膜外排泵。Rh123外排试验在常规操作中简便易行，因其对AML临床结局可能具有重要意义，可纳入MDR筛查。
