Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics

摘要

Acute myeloid leukemia (AML) is a heterogeneous group of dis- eases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34~+ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34~+ cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32/100 on average, suggesting gene-dosage effects underlying AML+8. Systematic analysis by cellular function indicated up- regulation of genes involved in cell adhesion in both groups of AML compared with CD34~+ blasts from normal individuals. Per- haps most interestingly, apoptosis-regulating genes were signifi- cantly down-regulated in AML+8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences.