Protein kinase CK2 sustains acute myeloid leukemia cell growth, however, its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic  and regulatory β subunits are consistently expressed in leukemia stem cells isolated from acute myeloid leukemia patients and cell lines. CK2 inactivation with the selective inhibitor CX-4945 or RNA interference induced an accumulation of leukemia stem cells in the late S-G2-M phases of the cell cycle and triggered late-onset apoptosis. As a result leukemia stem cells displayed an increased sensitivity to the chemotherapeutic agent doxorubicin. From a molecular standpoint, CK2 blockade was associated to a down-modulation of the stem cell-regulating protein BMI-1 and a marked impairment of AKT, NF-κB and STAT3 activation, while FOXO3a nuclear activity was induced. Notably, combined CK2 and either NF-κB or STAT3 inhibition resulted in a superior cytotoxic effect on leukemia stem cells. This study suggests that CK2 blockade could be a rational approach to minimize the persistence of residual leukemia cells.Leukemia accepted article preview online, 01 August 2016. doi:10.1038/leu.2016.209.

Protein kinase CK2 regulates AKT, NF-κB and STAT3 activation, stem cell viability and proliferation in acute myeloid leukemia

Brancalion, A;Manni, S;Mandato, E;Zaffino, F;Macaccaro, P;Carrino, M;Gianesin, K;Trentin, L;Zambello, R;Semenzato, G;Piazza, F
2017

Abstract

Protein kinase CK2 sustains acute myeloid leukemia cell growth, however, its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic  and regulatory β subunits are consistently expressed in leukemia stem cells isolated from acute myeloid leukemia patients and cell lines. CK2 inactivation with the selective inhibitor CX-4945 or RNA interference induced an accumulation of leukemia stem cells in the late S-G2-M phases of the cell cycle and triggered late-onset apoptosis. As a result leukemia stem cells displayed an increased sensitivity to the chemotherapeutic agent doxorubicin. From a molecular standpoint, CK2 blockade was associated to a down-modulation of the stem cell-regulating protein BMI-1 and a marked impairment of AKT, NF-κB and STAT3 activation, while FOXO3a nuclear activity was induced. Notably, combined CK2 and either NF-κB or STAT3 inhibition resulted in a superior cytotoxic effect on leukemia stem cells. This study suggests that CK2 blockade could be a rational approach to minimize the persistence of residual leukemia cells.Leukemia accepted article preview online, 01 August 2016. doi:10.1038/leu.2016.209.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3206932
Citazioni
  • ???jsp.display-item.citation.pmc??? 23
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 44
social impact