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Gene expression profiles of acute leukemia and detection of new prognostic factors

急性白血病基因表达谱及新预后因素检测

基本信息

批准号：
13671059
负责人：
KOBAYASHI Tohru
金额：
$ 0.51万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671059/
关键词：
Gene expression profiling DNA microarray Acute promyelocytic leukemia AML without maturation acute myeloid leukemia myeloperoxidase MHC class II-related genes

项目摘要

Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 acute AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15 ; 17)(q22 ; ql2) (French-American-British or FAB-M3 with t(15 ; 17)) and AML without maturation (FAB M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate σ-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15 ; 17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15 ; 17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15 ; 17). Growth factor-binding protein 2 gene was down-regulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor β, folate receptor β, low affinity immunoglobulin γ, Fc receptor II C precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15 ; 17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality ; t(15 ; 17)(q22 ; ql2).

急性髓系白血病（AML）具有不同的亚群，其特征在于不同的成熟度和特异性染色体易位。为了深入了解AML中的基因表达活动，我们使用cDNA微阵列对21例急性AML样本进行了基因表达谱研究，重点关注具有特异性易位t（15 ; 17）的急性早幼粒细胞白血病。（q22 ; ql2）（法国-美国-英国或FAB-M3与t（15 ; 17））和AML未成熟（FAB M1），其特征在于形态学和表型上不成熟的AML母细胞和无复发性染色体异常。使用多变量σ-分类器算法，我们鉴定了33个强特征基因，其将具有t（15 ; 17）的FAB-M3与其他AML样品区分开，以及24个强特征基因，其将FAB-M1分类。将具有t（15 ; 17）的FAB-M3与FAB-M1进行直接比较，筛选出13个强特征基因。这些基因包括一些已知与白血病发生和细胞分化有关的基因。ras通路中的基因RIN 1在FAB-M3中上调，具有t（15 ; 17）。生长因子结合蛋白2基因在FAB-M1中表达下调。FAB-M1中Huntingtin基因表达上调。其他包括多配体蛋白聚糖4、白细胞介素-2受体β、叶酸受体β、低亲和力免疫球蛋白γ、Fc受体II C前体、胰岛素样生长因子结合蛋白2和髓过氧化物酶，它们参与细胞分化。与FAB-M1细胞相比，具有t（15 ; 17）的FAB-M3细胞中髓过氧化物酶的过表达与常规细胞化学染色模式一致。因此，该研究揭示了形态学定义的FAB-M1亚型具有独特的基因表达特征，其有助于其细胞分化和增殖，以及FAB-M3具有复发性细胞遗传学异常; t（15 ; 17）（q22 ; q12）。