DNA microarray screening of differential gene expression in bone marrow samples from AML, non-AML patients and AML cell lines.
This study used cDNA microarray technology to compare gene expression profiles in acute myeloblastic leukaemia (AML) with cDNA dot-blot and real time PCR analysis of cDNA transcripts to confirm array data. Patient AML marrow samples and AML cell lines were compared with normal/non-AML samples. Screening revealed five particular genes to be significantly differentially expressed across the sample groups. The migration-inhibitory factor-related-proteins 8 and 14 (MRP-8 and MRP-14) genes, the products of which inhibit cell migration and differentiation were the most highly expressed in non-malignant cells. The high-mobility-group-protein gene (HMG-1) was up regulated in leukaemic samples and cell lines, which may be associated with aggressive disease. Also upregulated in malignant samples were genes encoding c-myc and glutathione-S-transferase pi (GSTP), the latter implicated in chemotherapy resistance. Faulty expression of such genes may contribute to the pathogenesis of AML and resistance to treatment.
Court
Emma Louise
EL
Centre for Research in Biomedicine, University of the West of England, Bristol BS16 1QY, UK.
Smith
M Ann
MA
Avent
Neil David
ND
Hancock
John T
JT
Morgan
Lyn M
LM
Gray
Atherton G
AG
Smith
J Graham
JG
D000328:Adult; D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D024243:HMGB1 Protein; D008263:Macrophage Migration-Inhibitory Factors; D016271:Proto-Oncogene Proteins c-myc; D005982:Glutathione Transferase