Enhanced CML stem cell elimination in vitro by bryostatin priming with imatinib mesylate.

Posted by rob on October 15, 2005 under Uncategorized | Be the First to Comment

Jørgensen HG, Allan EK, Mountford JC, Richmond L, Harrison S, Elliott MA, Holyoake TL

Exp Hematol. 2005 Oct ; 33(10): 1140-6

OBJECTIVE: In chronic myeloid leukemia (CML), imatinib mesylate (IM; Gleevec, Glivec) induces a G0/G1 cell-cycle block in total CD34(+) cells without causing significant apoptosis. Bryostatin-1 (bryo), a protein kinase C (PKC) modulator, was investigated for its ability to increase IM-mediated apoptosis either through induction of cycling of G0/G1 Ph(+) cells or antagonism of the IM-induced cell-cycle block. METHODS: The Ph(+) K562 cell line and primary CD34(+) CML cells were studied for cell-cycle progression (PI staining), proliferation ((3)H thymidine uptake), and survival (dye exclusion). RESULTS: Following 48 hours exposure to IM, on average more than 80% of surviving K562 cells were in G0/G1 as compared to approximately 50% for untreated control cultures (p

Enhanced CML stem cell elimination in vitro by bryostatin priming with imatinib mesylate.