Background/aim: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells.
Materials and methods: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting.
Results: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis.Artemisinin acted only on Jurkat cells. BMI1 inhibitors and BMI1-specific siRNA down-regulated the expression of NOTCH signaling proteins NOTCH1, HES1, and MYC. All but one cell lines did not have the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene targeted by BMI1, thus the inhibitors acted through CDKN2A-independent pathways.
Conclusion: BMI1 inhibition suppressed proliferation of leukemia cells through NOTCH signaling which functions downstream of BMI1, suggesting that BMI1 inhibitors can be candidate targeted drugs against leukemia.
Keywords: BMI1; CDKN2A; NOTCH; leukemia.
Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.