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

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）。

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).