Kohlmann Alexander, Schoch Claudia, Schnittger Susanne, Dugas Martin, Hiddemann Wolfgang, Kern Wolfgang, Haferlach Torsten
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians-University, Munich, Germany.
Genes Chromosomes Cancer. 2003 Aug;37(4):396-405. doi: 10.1002/gcc.10225.
Accurate subclassification of leukemia and the identification of prognostic determinants are essential to guide therapy and to improve patients' outcome. According to present standards, pre-therapeutic assessment depends on a combination of different methods. We aimed to expand the molecular characterization of different acute leukemia subtypes to identify new genome-wide diagnostic markers. Total RNA from 90 adult patients suffering from acute lymphoblastic leukemia (ALL, n = 25) and acute myeloid leukemia (AML, n = 65) was extracted at diagnosis and high density oligonucleotide microarrays were used to analyze the expression profiles of 12,000/22,000 genes in all specimens (Affymetrix U95Av2/U133A). All cases were thoroughly characterized by individual combinations of cytomorphology, cytogenetics, multiparameter immunophenotyping, and molecular genetics. The expression signature of a small set of differentially expressed genes was sufficient to accurately discriminate eight clinically relevant acute leukemia subgroups. Underlying chromosomal aberrations or immunophenotypical characteristics were strictly correlated with a distinct gene expression pattern for AML with t(8;21), t(15;17), t(11q23)/MLL, or inv(16) as well as for precursor B-ALL with t(9;22), t(8;14), or t(11q23)/MLL and precursor T-ALL. These data support a possible future application of microarray technology for classification of the acute leukemias.
白血病的准确亚分类及预后决定因素的鉴定对于指导治疗和改善患者预后至关重要。根据目前的标准，治疗前评估依赖于多种不同方法的联合使用。我们旨在扩展不同急性白血病亚型的分子特征描述，以鉴定新的全基因组诊断标志物。在诊断时从90例成年急性淋巴细胞白血病（ALL，n = 25）和急性髓系白血病（AML，n = 65）患者中提取总RNA，并使用高密度寡核苷酸微阵列分析所有标本中12,000/22,000个基因的表达谱（Affymetrix U95Av2/U133A）。所有病例均通过细胞形态学、细胞遗传学、多参数免疫表型分析和分子遗传学的个体化组合进行全面特征描述。一小部分差异表达基因的表达特征足以准确区分八个临床相关的急性白血病亚组。潜在的染色体畸变或免疫表型特征与t(8;21)、t(15;17)、t(11q23)/MLL的AML以及inv(16)的AML，以及t(9;22)、t(8;14)或t(11q23)/MLL的前体B-ALL和前体T-ALL的独特基因表达模式严格相关。这些数据支持微阵列技术未来可能用于急性白血病的分类。
