Hiçsönmez G, Erdemli E, Tekelioglu M, Tuncer A M, Ozbek N, Cetin M, Cotter T G
Department of Pediatric Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Leuk Lymphoma. 1996 Jun;22(1-2):91-6,follow.186,color plate VII-III. doi: 10.3109/10428199609051733.
We have previously demonstrated that various subtypes of AML children respond to high-dose methylprednisolone (HDMP; 20-30 mg/kg/day) which could induce in vivo differentiation of myeloid leukemic cells to mature granulocytes. In this study we have evaluated whether apoptosis occurs in AML cells of patients treated by HDMP using morphological criteria. For light and electron microscopic examination bone marrow aspirates were obtained four days and two weeks after methylprednisolone (30 mg/kg/day) treatment from two children with newly diagnosed AML (AML-M3 and AML-M4). In both patients maturation of leukemic cells has previously been reported four days (in patient with AML-M3) and two weeks (in patient with AML-M4) after HDMP treatment. Electron microscopy revealed the characteristic ultrastructural changes of various stages of apoptosis four days after HDMP treatment in a case with AML-M3. Morphologic evidence of apoptosis induced by HDMP were also detected on Wright-stained and toluidine blue stained semithin sections of BM preparations in a patient with AML-M4 and AML-M3 respectively. These findings suggest that HDMP which could induce in vivo terminal differentiation in myeloid leukemic cells is also able to induce apoptosis in patients with AML. The possibility of HDMP-induced apoptosis should be evaluated in a larger series of patients with AML and other types of malignant tumors.
我们之前已经证明，急性髓系白血病（AML）患儿的各种亚型对大剂量甲基泼尼松龙（HDMP；20 - 30 mg/kg/天）有反应，该药物可诱导骨髓白血病细胞在体内分化为成熟粒细胞。在本研究中，我们使用形态学标准评估了接受HDMP治疗的AML患者细胞中是否发生凋亡。为进行光镜和电镜检查，在两名新诊断为AML（AML-M3和AML-M4）的患儿接受甲基泼尼松龙（30 mg/kg/天）治疗后的第4天和第2周获取骨髓穿刺液。在这两名患者中，之前均报告在HDMP治疗后的第4天（AML-M3患者）和第2周（AML-M4患者）白血病细胞出现成熟。电镜显示，在1例AML-M3患者中，HDMP治疗4天后出现了凋亡各阶段的特征性超微结构变化。在1例AML-M4和AML-M3患者中，分别在骨髓标本的瑞氏染色和甲苯胺蓝染色半薄切片上也检测到了HDMP诱导凋亡的形态学证据。这些发现表明，能够诱导骨髓白血病细胞在体内终末分化的HDMP，也能够诱导AML患者细胞凋亡。HDMP诱导凋亡的可能性应在更多的AML患者及其他类型恶性肿瘤患者中进行评估。
