Molecular biological analysis of myelodysplastic syndrome of the childhood onset using DNA microarray method

利用 DNA 微阵列方法对儿童期发病的骨髓增生异常综合征进行分子生物学分析

• 批准号: 14570739
• 负责人: KAMACHI Yoshiro
• 金额: $ 1.73万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570739/
• 关键词: DNA microarray; childhood; myelodysplastic syndrome; juvenile myelomonocytic leukemia; leukemoid reaction; CD34 positive cell; ウイルス感染

We have very difficult cases to distinguish juvenile myelomonocytic leukemia (JMML) of the infancy with leukemoid reaction by virus infection, because we have not yet established useful diagnostic method to differentiate between these two diseases. In this study, we analyzed the gene expression pattern of CD34^+ cells of the bone marrow of patients with JMML using DNA microarray method. We extracted RNA from CD34^+ cells of the bone marrow of JMML patients before and after treatment. We applied amplified cRNA labeled with fluorescent to DNA microarray slide. We found that the expression level of FRAP(FKBP-rapamycin associated protein) and Syk(spleen tyrosine kinase) increased significantly after treatment and that the expression level of c-jun, TGF-beta receptor III(transforming growth factor-beta receptor III) and IL-2(interleukin 2) decreased significantly after treatment. All of these five genes are involved with intracellular signal transduction, transformation, differentiation, and propagation. We conclude that DNA microarray method is useful for examination of a change of gene expression in JMML patients before and after treatment.

由于尚未建立有效的诊断方法来鉴别病毒感染引起的幼年型髓单核细胞白血病（JMML）与类白血病反应，因此很难鉴别这两种疾病。本研究应用基因芯片技术分析了JMML患者骨髓CD 34 ^+细胞的基因表达谱。我们从JMML患者治疗前后的骨髓CD 34 ^+细胞中提取RNA。我们将扩增的cRNA用荧光标记到DNA微阵列载玻片上。我们发现FRAP（FKBP-雷帕霉素相关蛋白）和Syk（脾酪氨酸激酶）的表达水平在治疗后显著增加，而c-jun、TGF-β受体III（转化生长因子-β受体III）和IL-2（白细胞介素2）的表达水平在治疗后显著降低。所有这五个基因都参与细胞内信号转导、转化、分化和繁殖。我们的结论是，DNA微阵列方法是有用的检查基因表达的变化，在JMML患者治疗前后。

项目成果

Kojima S. et al.: "Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children."Blood. 100. 786-790 (2002)

Kojima S.等人：“儿童免疫抑制治疗后获得性再生障碍性贫血演变为骨髓增生异常综合征和急性髓系白血病的危险因素。”血液。

Manabe A, Kojima S, et al.: "Allogeneic hematopojetic stem cell trransplantaton for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the international JMML working Group"Leukemia. 16. 645-649 (2002)

Manabe A、Kojima S等人：“对27例根据国际JMML工作组的标准诊断为幼年型粒单核细胞白血病的儿童进行同种异体造血干细胞移植”白血病。

Manabe A, Kojima S. et al.: "Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the international JMML Working Group"Leukemia. 16. 645-649 (2002)

Manabe A、Kojima S.等人：“对27名根据国际JMML工作组标准诊断为幼年型粒单核细胞白血病的儿童进行同种异体造血干细胞移植”白血病。

Ohara A, Kojima S, et al: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"Br J Haematol. 116. 999-1010 (2002)

Ohara A、Kojima S 等人：“肝炎相关再生障碍性贫血儿童中骨髓增生异常综合征和急性髓性白血病的演变”Br J Haematol。

Ohara A, Kojima S. et al.: "Evolution of myelodysplastic syndrome and acute myelogenous leukaemia in children with hepatitis-associated aplastic anaemia"Br J Haematol. 116. 999-1010 (2002)

Ohara A、Kojima S. 等人：“肝炎相关再生障碍性贫血儿童中骨髓增生异常综合征和急性髓性白血病的演变”Br J Haematol。