Kaspers G J, Kardos G, Pieters R, Van Zantwijk C H, Klumper E, Hählen K, de Waal F C, van Wering E R, Veerman A J
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Leukemia. 1994 Jul;8(7):1224-9.
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.
儿童急性淋巴细胞白血病（ALL）的预后优于急性非淋巴细胞白血病（ANLL），且常观察到髓系抗原（MyAg）阴性ALL的预后优于MyAg阳性ALL，这可能与细胞耐药性差异有关。因此，我们用MTT法比较了125个ALL样本和28个ANLL样本对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位数比ANLL样本高75倍以上（p < 0.00001），对长春新碱的敏感性高2倍（p = 0.05）。其他药物的差异不显著。MyAg阴性ALL样本对糖皮质激素的敏感性高于MyAg阳性ALL样本（p ≤ 0.04）。泼尼松龙以及若进行测试的地塞米松，对36%的ANLL白血病细胞存活有刺激作用，但对ALL样本仅有2%有此作用（p < 0.0001）。长春新碱以及若进行测试的长春地辛，对11%的ANLL和4%的ALL样本有类似作用（p = 0.11）。我们得出结论，儿童ALL对联合化疗的反应比ANLL更有利，可能是由于ALL中糖皮质激素和长春新碱的抗白血病活性更高，而在ANLL中没有一种药物活性更高。同样，MyAg阴性ALL比MyAg阳性ALL预后更好，可能是由于对糖皮质激素相对敏感。糖皮质激素和长春花生物碱在部分样本中诱导白血病细胞增殖，最常见于ANLL。这些发现可能有助于设计针对ALL和ANLL的新化疗方案。
