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短疗程大剂量类固醇对一名急性巨核细胞白血病患儿白血病细胞成熟和凋亡的潜在影响。

The potential effect of short-course high-dose steroid on the maturation and apoptosis of leukemic cells in a child with acute megakaryoblastic leukemia.

作者信息

Hiçsönmez Gönül, Cetin Mualla, Okur Hamza, Erdemli Esra, Gürgey Aytemiz

机构信息

Department of Pediatric Hematology, Faculty of Medicine, Ihsan Doğramaci Children's Hospital, Hacettepe University, 06100, Ankara, Turkey.

出版信息

Leuk Lymphoma. 2003 Jun;44(6):1037-42. doi: 10.1080/1042819031000067954.

Abstract

High-dose methylprednisolone (HDMP) treatment has been shown to induce differentiation of myeloid leukemic cells in children with acute promyelocytic leukemia and other subtypes (FAB AML M1-M2-M4) of acute myeloblastic leukemia. In the present study, a child with acute megakaryoblastic leukemia (AMKL) was given HDMP (30 mg/kg/day) orally in a single dose for the first 4 days of induction therapy. A marked decrease in peripheral blood blast cells and an increase in platelet count associated with a striking change in bone marrow (BM) morphology was observed following a short-course of HDMP treatment alone. BM cells developed distinct morphology characterized by cytoplasmic blebbing and some appeared as platelet producing micromegakaryocytes. Flow cytometric analysis of the BM cells 4 days after HDMP treatment demonstrated a decrease in the percentage of cells co-expressing CD34 and CD117 antigens and a marked increase in CD42a antigen. These changes in BM morphology and immunophenotype may suggest maturation effect of HDMP on megakaryocytic leukemic cells. In addition ultrastructural analysis of BM cells cultured with methylprednisolone (10(-3) and 10(-6) M) for 24 and 48 h showed numerous apoptotic cells. This was coincident with a significant increase in the percentage of annexin positive cells. These results suggest that HDMP treatment may induce differentiation and apoptosis of leukemic cells in a child with AMKL and it could be a promising agent for remission induction of patients with AMKL.

摘要

大剂量甲基泼尼松龙(HDMP)治疗已被证明可诱导急性早幼粒细胞白血病患儿以及急性髓细胞白血病其他亚型(FAB AML M1 - M2 - M4)的髓系白血病细胞分化。在本研究中,一名急性巨核细胞白血病(AMKL)患儿在诱导治疗的前4天接受单剂量口服HDMP(30 mg/kg/天)。单独进行短疗程HDMP治疗后,观察到外周血原始细胞显著减少,血小板计数增加,同时骨髓(BM)形态发生显著变化。BM细胞呈现出独特的形态,其特征为细胞质起泡,有些表现为产生血小板的微巨核细胞。HDMP治疗4天后对BM细胞进行流式细胞术分析显示,共表达CD34和CD117抗原的细胞百分比降低,而CD42a抗原显著增加。BM形态和免疫表型的这些变化可能提示HDMP对巨核细胞白血病细胞具有成熟作用。此外,用甲基泼尼松龙(10(-3)和10(-6) M)培养BM细胞24小时和48小时后的超微结构分析显示有大量凋亡细胞。这与膜联蛋白阳性细胞百分比的显著增加相一致。这些结果表明,HDMP治疗可能诱导AMKL患儿白血病细胞的分化和凋亡,并且它可能是AMKL患者缓解诱导的一种有前景的药物。

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