Multifaceted actions of 8-amino-adenosine kill BCR-ABL positive cells.

ABSTRACT: Survival of chronic myelogenous leukemia (CML) cells is dependent on BCR-ABL kinase, the activity of which is contingent on the level of BCR-ABL protein and the availability of adenosine triphosphate (ATP). We hypothesized that 8-amino-adenosine (8-amino-Ado)-mediated reduction in cellular ATP level and inhibition of mRNA synthesis leading to a decrease in protein level would result in a multifaceted targeting of BCR-ABL. Using K562 cells, we demonstrated that there was a dose- and time-dependent increase in 8-amino-ATP accompanied by a > 95% decline in the endogenous ATP pool. In parallel, 8-amino-Ado inhibited RNA synthesis and resulted in a depletion of BCR-ABL transcript. Consistent with this, BCR-ABL and ABL protein levels were also decreased. These effects were associated with the in

SUBMITTER: Pillai RN 

PROVIDER: S-EPMC5648543 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature