Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis.
OBJECTIVE
Translocation-associated gene fusions are well recognized in acute myeloid leukemia. Other molecular genetic changes are less well known. The novel cDNA technology has opened the avenue to large-scale gene expression analysis. Our aim was to perform cDNA microarray analysis of acute myeloid leukemia (AML).


METHODS
We performed cDNA microarray analysis using the Clontech hematology filter (containing 406 genes) on 15 patients to study gene expression profiling in AML. As reference, we used whole bone marrow from 5 healthy donors.


RESULTS
Our results revealed 50 differentially expressed genes in at least 3 out of 15 patients. Twenty-two genes were upregulated (ratio > or =4), whereas 28 genes were downregulated (ratio < or =0.25). All but one of the 13 genes tested by real-time polymerase chain reaction (PCR) showed the same expression profiles. Among the overexpressed genes, several were those earlier associated with chromosomal translocations and gene fusions. These genes were FGFR1, MYC, NPM1, DEC, and BCL2. The expression of two upregulated genes, HOXA4 and CSF1R, was significantly higher in patients with a white blood cell count higher than 30 x 10(9)/L cells. In patients whose white blood cell count was higher than 100 x 10(9)/L cells, both CLC and GRN were significantly underexpressed, whereas HOXA4 and DAPK1 were overexpressed. FGFR1 and CAMLG were more frequently significantly overexpressed in patients with CD56 immunophenoytpe.


CONCLUSIONS
Clinical and prognostic significance of differential gene expression should be studied with a larger series of patients by using other techniques, such as quantitative real-time PCR.
Larramendy
Marcelo L
ML
Department of Pathology, Haartman Institute, Helsinki University Central Hospital, FIN-00014 University of Helsinki, Haartmaninkatu 3, Helsinki, Finland.
Niini
Tarja
T
Elonen
Erkki
E
Nagy
Bálint
B
Ollila
Juha
J
Vihinen
Mauno
M
Knuutila
Sakari
S
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D064550:Death-Associated Protein Kinases; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D000090243:Nucleophosmin; D015513:Oncogene Proteins / Q000235:genetics; D009857:Oncogenes / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D000077153:Progranulins; D012313:RNA / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D014178:Translocation, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C089404:CAMLG protein, human; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000077153:Progranulins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D014764:Viral Proteins; D000090243:Nucleophosmin; C073547:HOXA4 protein, human; D012313:RNA; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D016186:Receptor, Macrophage Colony-Stimulating Factor; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases