STI571 For Bone Marrow Purging Ex Vivo In Chronic Myeloid Leukemia

Imatinib Mesylate (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase, can selectively induce apoptosis in Bcr-Abl-positive cells and suppress their proliferation and colony formation. In this study, STI571 was used for ex vivo purging of marrow of chronic myeloid leukemia(CML). Marrow cells from CML patients in complete remission and marrow cells from normal subject mixed with K562 cells simulated human remission marrow were treated with STI571. We found STI571 could significantly supress the proliferation and colony formation of leukemia cells and induce apoptosis without affecting the growth of the normal cells. So, STI571 could result in a substantial enrichment for Ph-negtive cells. Meanwhile, to overcome the resistance of K562 cells to STI571 and potentiate it's effects, we treated K562 cells with STI571 in combination with Cyclooxygenase-2 (COX-2) inhibitor ,Celecoxib. We found that the combination of STI571 with Celecoxib could dramatically suppress the proliferation of K562 cells and significantly promoted the apoptosis induced by STI571. Furthermore, several apoptosis-regulated and proliferation-related gene and ptotein were involved in this action including down-regulation of cox-2, IL-6, bcl-2 gene and Bcl-2, P210 protein. In conclusion, STI571 could serve as an agent for ex vivo purging of CML marrow which may be enhanced by adding COX-2 inhibitor. STI571 in combination with COX-2 inhibitor may be more effective for purging of CML marrow and may be used for CML patients with resistant disease.