Combined genetic and transcriptional profiling of acute myeloid leukemia with normal and complex karyotypes.
OBJECTIVE
Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Patients with a normal karyotype constitute the largest single group; multiple chromosome rearrangements involving three or more chromosomes occur in 5 10% of AML patients. The pathophysiologic mechanisms underlying both groups are largely unknown. In the current study, we have systematically combined transcriptional profiles with cytogenetic data from 15 AML patients with either normal or complex karyotypes.


METHODS
The expression profiles were investigated by unsupervised hierarchical clustering, supervised cluster analysis, and comparative genomic microarray analysis. In addition, the samples were analyzed by G-banding and/or spectral karyotyping and comparative genomic hybridization.


RESULTS
Our results show that AML with complex karyotypes exhibit a gene expression profile that is specific to this group of patients. The differentially expressed genes included several located on 5q and 7q, as well as genes involved in controlling cell division. We also found that DNA gains and losses caused by multiple chromosome rearrangements result in altered gene expression in a gene-dosage-dependent manner.


CONCLUSIONS
These data provide insight into the mechanisms of multiple chromosome rearrangements and further demonstrate that the expression patterns of AML are strongly linked to the karyotypic status, even for the relatively undefined cytogenetic subgroup AML with complex karyotype.
Lindvall
Charlotta
C
Department of Molecular Medicine, Karolinska Hospital and Institutet, Stockholm, Sweden. charlotta.lindvall@vai.org <charlotta.lindvall@vai.org>
Furge
Kyle
K
Björkholm
Magnus
M
Guo
Xiang
X
Haab
Brian
B
Blennow
Elisabeth
E
Nordenskjöld
Magnus
M
Teh
Bin Tean
BT
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D032681:Spectral Karyotyping; D014158:Transcription, Genetic
D018076:DNA, Complementary; D009363:Neoplasm Proteins