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

Abstract：

:Protein kinase CK2 sustains acute myeloid leukemia cell growth, but its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic α 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 with a downmodulation of the stem cell-regulating protein BMI-1 and a marked impairment of AKT, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) activation, whereas 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.

journal_name

Leukemia

journal_title

Leukemia

authors

Quotti Tubi L,Canovas Nunes S,Brancalion A,Doriguzzi Breatta E,Manni S,Mandato E,Zaffino F,Macaccaro P,Carrino M,Gianesin K,Trentin L,Binotto G,Zambello R,Semenzato G,Gurrieri C,Piazza F

doi

10.1038/leu.2016.209

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

292-300

issue

2

eissn

0887-6924

issn

1476-5551

pii

leu2016209

journal_volume

31

pub_type

杂志文章

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