Abstract
Objective: To explore the effects of STI571 on the expression of c-kit gene of the bone marrow mononuclear cells from patients with acute non-lymphocytic leukemia (ANLL) and to study the gene difference expression in original leukemia cells from the bone marrow of ANLL patients with CD117 overexpress treated by STI571, so as to explore initially the mechanism of the restraint of proliferation caused by STI571.
Methods: The expression of CD117 and C-kit mRNA level were assayed by FACS and RT-PCR before and after different concentration STI571 cultivatio. The changes of gene expression were examined with the cDNA array in original leukemia cells after treated by STI571 and control.
Results: After STI571 treatment, the expression of CD117 and the mRNA expression of c-kit were significantly lower than before (P<0.05). There were over 730 different genes in each pair of chips, in which 156 different genes expressed together. In all different genes, 66.67% (104/156) were up-regulated, 33.33% (52/156) were down-regulated. Cellular skeleton accounted to 4.49% (7/156), oncogenes and tumor supressors 6.41% (10/156), cells receptor 7.05% (11/156), extracellular signal transduction proteins 23.07% (36/156), cyclin proteins7.05% (11/156), apoptosis correlation proteins 1.92% (3/156) and other genes accounted to50% (78/156). Genes with over ten times relative difference amounted to 26.92% (42/156).
Conclusion: The restraint of c-kit on ANLL fresh cells was related to concentration of STI571. The mechanism of the restraint of proliferation caused by STI571 may relate to three ways: 1. STI571 realizes its biological function by affecting different signal conduction pathways through protein tyrosine kinase, guanine-nucleotide-binding protein and protein kinase C; 2. STI571 restrains the infinite differentiation of cells through affecting of tumor cellular mitosis; 3. Destroy cellular skeleton.
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