POSTER NO: 433

Gene Expression Networks Underlying BCR-ABL Induced Malignancy

Keshen Li, Dahai Zhu
Molecular and Cellular Developmental Biology Laboratory, Harbin Institute of Technology, P O Box 437# Harbin Institute of Technology, Harbin P R China

Chronic myeloid leukemia (CML) is probably the best understood human malignancy which is caused by a BCR-ABL fusion gene on the Ph chromosome. The BCR-ABL chimeric protein with its constitutive tyrosine kinase activity is thought to play a central role in the leukemogenesis. However, only a few BCR-ABL downstream target genes which are essential for malignant transformation have been identified so far. Our work is to use the Ph positive CML cell line and STI571, a newly designed molecule which selectively inhibits the BCR-ABL PTK activity, to study the molecular mechanism of BCR-ABL induced transformation and to define the downstream targets and multiple signaling pathways regulated by BCR-ABL. In this study, Gene expression alterations in the CML cell line K562 before and after STI571 treatment were analyzed using differential-display PCR and several differentially expressed bands were obtained and subjected to further analysis; cDNA microarray is also under designing in order to give a more global analysis of transcriptional regulation in Ph positive cells. All of the data from our work may contribute to the further research on the gene function and the functional network which contribute to the abnormal biological behavior of Ph positive cells.