Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles - PubMed (original) (raw)

Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles

Claudia Schoch et al. Proc Natl Acad Sci U S A. 2002.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous group of genetically defined diseases. Their classification is important with regard to prognosis and treatment. We performed microarray analyses for gene expression profiling on bone marrow samples of 37 patients with newly diagnosed AML. All cases had either of the distinct subtypes AML M2 with t(8;21), AML M3 or M3v with t(15;17), or AML M4eo with inv(16). Diagnosis was established by cytomorphology, cytogenetics, fluorescence in situ hybridization, and reverse transcriptase-PCR in every sample. By using two different strategies for microarray data analyses, this study revealed a unique correlation between AML-specific cytogenetic aberrations and gene expression profiles.

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Figures

Figure 1

Figure 1

Three cytogenetically defined AML subtypes with t(15;17), t(8;21), or inv(16) can be separated based on their gene expression profiles of 1,000 preselected genes. The three different subgroups form distinct clusters. For visualization in a two-dimensional plot the first two principal components were chosen as they captured most of the variation in the original data set. The subgroups are colored according to their chromosomal aberrations.

Figure 2

Figure 2

Hierarchical cluster analysis of the gene expression pattern of the set of 13 predictor genes as identified according to the adapted class prediction methodology introduced by Golub et al. (13). The three distinct cytogenetic AML subgroups can clearly be separated based on their gene expression profiles. Each row represents a leukemia sample and each column a gene. GenBank accession numbers are shown on the top. Varying expression levels are shown on a scale from black (no gene expression) to bright red (highest expression). The subgroups are colored according to their chromosomal aberrations.

Figure 3

Figure 3

Schematic representation of the 15 decision trees (a_–_o) used in the multiple-tree classifier. Arrows indicate high (arrow up) or low (arrow down) expression, 0 and + denote absence or presence of a gene, respectively [e.g., in a the low expression of X96719 indicates AML with t(15;17) whereas the high expression of X96719 indicates AML with inv(16) or AML with t(8;21); the latter two entities are distinguished by X53742: lack of expression identifies AML with inv(16) and positive expression predicts AML with t(8;21)]. Accession numbers are given for relevant genes. Nodes are represented as ovals and leaves as rectangles. Classes are referred to as t(15;17), t(8;21), or inv(16).

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