Overexpression of translocation-associated fusion genes of FGFR1, MYC, NPM1, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis

Marcelo L. Larramendy, Tarja Niini, Erkki Elonen, Bálint Nagy, Juha Ollila, Mauno Vihinen, Sakari Knuutila

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Background and Objectives. 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). Design and 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 ≥ 4), whereas 28 genes were downregulated (ratio ≤ 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 30X109/L cells. In patients whose white blood cell count was higher than 100X109/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. Interpretation and 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.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalHaematologica
Volume87
Issue number6
Publication statusPublished - Jan 1 2002

Keywords

  • Acute myeloid leukemia
  • CDNA array
  • Fusion genes
  • Gene expression

ASJC Scopus subject areas

  • Hematology

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