Schlaifer D, Duchayne E, Demur C, Alvinerie P, Muller C, Attal M, Cooper M R, Payen C, Monsarrat B, Myers C E, Pris J, Laurent G
Service d'Hematologie, Clinique Dieulafoy, Hopital de Purpan, Toulouse, France.
Leuk Lymphoma. 1996 Feb;20(5-6):441-6. doi: 10.3109/10428199609052426.
Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.
髓过氧化物酶（MPO）已被证明可在体外催化长春新碱（VCR）的降解。鉴于MPO是一种溶酶体酶，正常活化的髓样细胞和白血病髓样细胞均可将其释放到循环系统中，我们研究了急性髓细胞白血病（AML）患者的血清是否可能具有增强的VCR降解能力。使用高效液相色谱法（HPLC）对31份血清样本（23份来自急性髓细胞白血病患者，8份来自患有其他病症的患者）与（³H）VCR孵育后进行分析。与正常血清或淋巴白血病患者的血清相比，AML患者的血清显示出更强的VCR分解能力。向血清中添加MPO的电子供体过氧化氢可显著增加VCR的降解，而添加1 mM对乙酰氨基酚（一种MPO抑制剂）则几乎完全抑制VCR的降解。在过氧化氢存在下的VCR过氧化作用与采集血清时循环系统中白血病原始细胞的数量以及通过免疫测定法测定的血清MPO浓度均相关。这些数据表明，AML中VCR的失活可能部分归因于白血病髓母细胞的MPO将其快速过氧化为无活性物质。
