Chronic myelogenous leukemia molecular signature.
To obtain comprehensive information about the genes involved in BCR/ABL-dependent leukemogenesis, samples from 15 chronic myelogenous leukemia (CML) patients and seven normal donors were analysed using a cDNA microarray assay. After subtraction of the artificial, random or cross-hybridization signals, data about 5315 genes have been effectively analysed in all samples. The assay revealed >/=4-fold difference in the average expression of 263 genes in all CML samples when compared to normal counterparts, with 148 genes being upregulated and 115 being downregulated. Differentially expressed genes include those associated with BCR/ABL-induced abnormalities in signal transduction, gene transactivation, cell cycle, apoptosis, adhesion, DNA repair, differentiation, metabolism and malignant progression. Interestingly, CML-blast crisis cells in peripheral blood differ from those from bone marrow, indicating major changes in gene expression profiles upon entering into the bloodstream. Moreover, BCR/ABL modulates expression of genes, which are involved in regulation of chromosome/chromatin/DNA dynamics during S and M cell cycle phase. Moreover, the ability of CML cells to recognize and respond to a pathogen infection may be compromised. Altogether, this work provides a large body of information regarding gene expression profiles associated with CML and also represents a source of potential targets for CML therapeutics.
Nowicki
Michal Oskar
MO
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Pawlowski
Peter
P
Fischer
Thomas
T
Hess
Georg
G
Pawlowski
Tomasz
T
Skorski
Tomasz
T
D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002453:Cell Cycle; D018450:Disease Progression; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000145:classification / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013382:Subtraction Technique
D009363:Neoplasm Proteins; D016044:Fusion Proteins, bcr-abl