title: Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics.
abstract: Acute myeloid leukemia (AML) is a heterogeneous group of diseases. 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% 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. Perhaps most interestingly, apoptosis-regulating genes were significantly 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.
authors.affiliation: Division of Human Cancer Genetics and Division of Hematology/Oncology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: K
authors.initials: K
authors.lastname: Virtaneva
authors.forename: F A
authors.initials: FA
authors.lastname: Wright
authors.forename: S M
authors.initials: SM
authors.lastname: Tanner
authors.forename: B
authors.initials: B
authors.lastname: Yuan
authors.forename: W J
authors.initials: WJ
authors.lastname: Lemon
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: A
authors.initials: A
authors.lastname: de La Chapelle
authors.forename: R
authors.initials: R
authors.lastname: Krahe
mesh_terms: D000208:Acute Disease; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012016:Reference Values; D014314:Trisomy
chemical_list: D018952:Antigens, CD34