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

Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal c ytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy, How trisomy contribute s to tumorigenesis is unknown, We used oligonucleotide-based DNA microarray s to study global gene expression in AML+8 patients with +8 as the sole chr omosomal abnormality and AML-CN patients. CD34(+) cells purified from norma l bone marrow (BM) were also analyzed as a representative heterogeneous pop ulation of stem and progenitor cells. Expression patterns of AML patients w ere clearly distinct from those of CD34(+) cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML+8. Systematic ana lysis by cellular function indicated upregulation of genes involved in cell adhesion in both groups of AML compared with CD34(+) blasts from normal in dividuals. Perhaps most interestingly, apoptosis-regulating genes were sign ificantly down-regulated in AML+8 compared with AML-CN, We conclude that th e clinical and cytogenetic heterogeneity of AML is due to fundamental biolo gical differences.