Styczynski J, Wysocki M, Debski R, Czyzewski K, Balwierz W, Juraszewska E, Matysiak M, Malinowska I, Stanczak E, Sońta-Jakimczyk D, Szczepanski T, Wachowiak J, Konatkowska B, Balcerska A, Ploszynska A, Kowalczyk J, Stefaniak J, Badowska W, Wieczorek M, Olejnik I, Krawczuk-Rybak M, Kuzmicz M
Department of Pediatric Hematology and Oncology, Collegium Medicum Bydgoszcz UMK, Bydgoszcz 85-094, Poland.
Neoplasma. 2005;52(1):74-8.
Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.
核苷类似物如氟达拉滨和克拉屈滨用于治疗成人惰性淋巴瘤和白血病，而阿糖胞苷主要用于急性白血病的治疗方案。它们的作用机制基于对参与DNA、RNA和蛋白质合成的酶的抑制。本研究的目的是分析儿童急性淋巴细胞白血病（ALL）和髓细胞白血病（AML）的体外细胞药物敏感性。通过MTT试验，对从264例患者中分离出的白血病细胞进行了氟达拉滨、克拉屈滨和阿糖胞苷的细胞毒性测试，其中包括152例初发ALL、45例复发ALL、54例初发AML和13例复发AML。使50%受试细胞致死的药物浓度被视为耐药值。三种受试核苷类似物对初发ALL样本显示出最高的细胞毒性。复发ALL和初发AML样本比初发ALL样本更具耐药性。出乎意料的是，所有受试药物在初发AML和复发AML样本之间未观察到差异，这表明核苷类似物在复发AML中是活性药物，而复发AML通常被认为是耐药性疾病。所有受试药物在每个分析亚组中均表现出显著的交叉耐药性。总之，受试核苷类似物在复发阶段对儿童白血病表现出相对良好的活性。
