Different cellular drug resistance profiles in childhood lymphoblastic and non-lymphoblastic leukemia: a preliminary report.
Different cellular drug resistance profiles in childhood lymphoblastic and non-lymphoblastic leukemia: a preliminary report.
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发表时间：
1994-07
期刊：
影响因子：
11.4
通讯作者：
G. Kaspers;G. Kardos;R. Pieters;C. V. van Zantwijk;E. Klumper;K. Hählen;F. D. de Waal;E. V. van Wering-E.-V.
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作者：
G. Kaspers;G. Kardos;R. Pieters;C. V. van Zantwijk;E. Klumper;K. Hählen;F. D. de Waal;E. V. van Wering-E.-V.
儿童急性淋巴细胞白血病（ALL）预后好于急性非淋巴细胞白血病（ANLL），髓系抗原（MyAg）阴性的ALL预后好于MyAg阳性的ALL，这可能与细胞耐药的差异有关。因此，我们用MTT法比较了125例ALL和28例ANLL对12种药物的耐药性。ALL样本对糖皮质激素泼尼松龙和地塞米松的敏感性中值> 75倍（p < 0.00001），对长春新碱的敏感性中值> 2倍（p = 0.05）。其他药物的差异不显著。MyAg阴性的ALL样本比MyAg阳性的ALL样本对糖皮质激素更敏感（p <0.04）。泼尼松龙和地塞米松（如果进行测试）对36%的ANLL患者的白血病细胞存活有刺激作用，但对2%的ALL患者的白血病细胞存活有刺激作用（p < 0.0001）。如果进行测试，阿贝斯汀和长春地辛在11%的ANLL和4%的ALL样本中具有相似的效果（p = 0.11）。我们的结论是，更有利的反应对急性非淋巴细胞白血病的联合化疗的儿童可能是解释了较高的抗白血病活性的糖皮质激素和长春新碱在急性淋巴细胞白血病，而没有更积极的药物在急性非淋巴细胞白血病。同样，MyAg阴性ALL的预后优于MyAg阳性ALL，可能是由于对糖皮质激素的相对敏感性。糖皮质激素和长春花生物碱诱导部分样本中的白血病细胞增殖，最常见于ANLL。本研究结果可为急性淋巴细胞白血病（ALL）和急性非淋巴细胞白血病（ANLL）的化疗方案设计提供参考。
The better prognosis of acute lymphoblastic leukemia (ALL) than of acute non-lymphoblastic leukemia (ANLL) in children, and the often observed better prognosis of myeloid-antigen (MyAg) negative ALL than of MyAg-positive ALL, may be related to differences in cellular drug resistance. We therefore compared the resistance to 12 drugs of 125 ALL and 28 ANLL samples with the MTT assay. ALL samples were median > 75-fold more sensitive to the glucocorticoids prednisolone and dexamethasone (p < 0.00001), and 2-fold more sensitive to vincristine (p = 0.05) than ANLL samples. Differences for the other drugs were not significant. MyAg-negative ALL samples were more sensitive to glucocorticoids than MyAg-positive ALL-samples (p < or = 0.04). Prednisolone, and dexamethasone if tested, had a stimulatory effect on leukemic cell survival in 36% of ANLL, but in only 2% of ALL samples (p < 0.0001). Vincristine, and vindesine if tested, had a similar effect in 11% of ANLL, and in 4% of ALL samples (p = 0.11). We conclude that the more favorable response of ALL against ANLL to combination chemotherapy in children may be explained by the higher antileukemic activity of glucocorticoids and of vincristine in ALL, while none of the drugs was more active in ANLL. Similarly, the better prognosis of MyAg-negative ALL than of MyAg-positive ALL may be explained by a relative sensitivity to glucocorticoids. Glucocorticoids and vinca-alkaloids induced leukemia cell proliferation in part of the samples, most frequently in ANLL. The findings may be useful in the design of new chemotherapeutic regimens for ALL and ANLL.