Nara N, Chen G J, Murohashi I, Tohda S, Imai Y, Tomiyama J, Nagata K, Suzuki T, Tanikawa S, Shiina S
Department of Laboratory Medicine, Tokyo Medical and Dental University, Japan.
Exp Hematol. 1992 Aug;20(7):904-8.
The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology.
根据法美英(FAB)协作组分类的急性髓细胞白血病(AML)亚组之间,比较了白血病原始祖细胞的体外生长活性和药物敏感性。从AML患者外周血中分离出的白血病细胞在甲基纤维素培养基中培养,并测定原代集落(PE1)和再接种后的二代集落(PE2)的接种效率。PE1和PE2分别被认为反映了白血病原始祖细胞的终末分裂能力和自我更新能力。PE1和PE2在AML患者中各不相同;这些发现表明,就白血病细胞的增殖活性而言,AML是一种异质性疾病。PE1或PE2与AML亚型之间未发现显著相关性。在甲基纤维素和悬浮培养中研究了白血病原始祖细胞对阿糖胞苷(Ara-C)的敏感性。Ara-C敏感性与AML亚型也无显著相关性。相比之下,PE2与患者的缓解结局之间存在统计学上的显著相关性,而PE1与临床结局无显著关联。本研究结果表明,白血病原始祖细胞的增殖活性,尤其是自我更新能力,对AML患者的预后具有高度预测性,但与根据原始细胞形态分类的AML亚型无显著相关性。