Development of a new classification for AML based on the gene expression profile in leukemia stem cells.

根据白血病干细胞的基因表达谱开发新的 AML 分类。

• 批准号: 15390303
• 负责人: TOMONAGA Masao
• 金额: $ 3.01万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390303/
• 关键词: leukemia; gene expression profile; classification; dysplasia; myeloperoxidase; CD133; 形態的異形性

Gene expression profiles of AML with morphological dysplasia were analyzed using Affymetrix GeneChip HGU95Av2 microarrays aiming to develop a new classification system of AML. From (1) 11 cases of AML with trilineage dysplasia, (2) 15 cases of de novo AML without dysplasia and (3) 11 cases of AML following MDS, CD133 positive leukemia cells were separated and the expression of about 12000 genes was examined. Based on the expression profile of these genes, AML cases in category (1) and (3) were clearly separated with principal component. analysis. Although cases in category (1) and (3) have morphological dysplasia, they were shown to possess different biological backgrounds. During the analysis of gene expression, myeloperoxidase (MPO) gene seemed differentially expressed. Using real time quantitative PCR methods, the level of MPO gene expression was low among cases in category (1) compared to those in (2). The high level of MPO gene expression was associated wit better prognosis, suggesting that the classification of AML based on the gene expression was useful and meaningful. Another candidate gene, laminine receptor, also seemed t relate to the karyotype of AML cells. These observations suggested that the expression of those genes would be useful to classify certain cases of AML and they were important to see the insight of AML biology.

利用Affymetrix GeneChip HGU95Av2微阵列分析AML形态学异常的基因表达谱，旨在建立一种新的AML分类系统。从(1)11例伴有三期发育不良的AML、(2)15例未发生发育不良的新生AML和(3)11例MDS后的AML中分离出CD133阳性白血病细胞，检测了约12000个基因的表达。基于这些基因的表达谱，分类(1)和(3)AML病例与主成分明显分离。分析。虽然(1)类和(3)类的病例有形态发育不良，但它们具有不同的生物学背景。在基因表达分析中，髓过氧化物酶（MPO）基因表现出差异表达。采用实时定量PCR方法，与(2)相比，(1)类病例的MPO基因表达水平较低。高水平的MPO基因表达与较好的预后相关，提示基于基因表达的AML分类是有用和有意义的。另一个候选基因，层胺受体，似乎也与AML细胞的核型有关。这些观察结果表明，这些基因的表达将有助于对某些AML病例进行分类，并且它们对于了解AML生物学非常重要。

项目成果

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia

AC133阳性白血病细胞髓过氧化物酶基因的表达与急性髓系白血病的预后相关

• 发表时间: 2006
• 期刊: Leuk Res 30
• 作者: Taguchi J;Miyazaki Y;Tsutsumi C;Sawayama Y;Ando K;Tsushima H;Fukushima T;Hata T;Yoshida S;Kuriyama K;Honda S;Jinnai I;Mano H;Tomonaga M.
• 通讯作者: Tomonaga M.

DNA microarray analysis of dysplastic morphology associated with acute myeloid leukemia.

与急性髓系白血病相关的发育不良形态的 DNA 微阵列分析。

• 发表时间: 2004
• 期刊: Exp Hematol. 32
• 作者: Numata;A.;Shimoda;K.;Kamezaki;K.;Haro;T.;Kakumitsu;H.;Shide;K.;Kato;K.;Miyamoto;T.;Yamashita;Y.;Oshima;Y.;Nakajima;H.;Iwama;A.;Aoki;K.;Takase;K.;Gondo;H.;Mano;H.;Harada;M.;He H.et al.;Kaneda R. et al.;Tsutsumi C. et al.
• 通讯作者: Tsutsumi C. et al.

DNA microarray analysis of dysplastic morphology associated with acute myeloid leukemia

急性髓性白血病相关发育异常形态的 DNA 微阵列分析

• 发表时间: 2004
• 期刊: Exp Hematol 32
• 作者: Tsutsumi;C.;Ueda;M.;Miyazaki;Y.;Yamashita;Y.;Choi;Y.L.;Ota;J.;Kaneda;R.;Koinuma;K.;Fujiwara;S.;Kisanuki;H.;Ishikawa;M.;Ozawa;K.;Tomonaga;M.;Mano;H.
• 通讯作者: H.