Heterogeneous sensitivity of human acute myeloid leukemia to ?-catenin down-modulation.

ABSTRACT: Dysregulation of the Wnt/?-catenin pathway has been observed in various malignancies, including acute myeloid leukemia (AML), where the overexpression of ?-catenin is an independent adverse prognostic factor. ?-catenin was found upregulated in the vast majority of AML samples and more frequently localized in the nucleus of leukemic stem cells compared with normal bone marrow CD34(+) cells. The knockdown of ?-catenin, using a short hairpin RNA (shRNA) lentiviral approach, accelerates all-trans retinoic acid-induced differentiation and impairs the proliferation of HL60 leukemic cell line. Using in vivo quantitative tracking of these cells, we observed a reduced engraftment potential after xenotransplantation when ?-catenin was silenced. However, when studying primary AML cells, despite effective downregulation of ?-catenin we did not observe any impairment of their in vitro long-term maintenance on MS-5 stroma nor of their engraftment potential in vivo. Altogether, these results show that despite a frequent ?-catenin upregulation in AML, leukemia-initiating cells might not be 'addicted' to this pathway and thus targeted therapy against ?-catenin might not be successful in all patients.

SUBMITTER: Gandillet A 

PROVIDER: S-EPMC4289854 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature