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Novel players in multiple myeloma pathogenesis: role of protein kinases CK2 and GSK3.

Abstract：

:Multiple myeloma (MM) is an incurable plasma cell malignancy, which causes a significant morbidity due to organ damage and bone tissue destruction. In recent years, novel drugs have become available for MM therapy thanks to a more deepened knowledge of this disease's pathogenesis. The perspective of employing targeted therapies has considerably changed the expectations on the clinical outcome for patients affected by this malignancy and among the targetable molecules identified for MM therapy are several protein kinases, which have been proven to play relevant roles in supporting malignant plasma cell growth by regulating critical signaling cascades and by sustaining oncogenic mechanisms. Protein kinase CK2 (formerly known as casein kinase 2) and GSK3 (glycogen synthase kinase 3) are two multifaceted serine-threonine kinases whose task in the pathogenesis of malignant cell growth is increasingly emerging both in solid and blood tumors. In hematologic malignancies, CK2 and GSK3 have been shown to play an oncogenic function in chronic and acute leukemias as well as in MM. They have been demonstrated to act by impinging on pivotal signaling pathways that control malignant clone growth. We will herein briefly review the more recent advancements on the role of these two kinases in regulating the NF-κB, STAT3 and endoplasmic reticulum (ER) stress/unfolded protein response (UPR) signaling in MM and discuss the rationale of using small selective inhibitors as a therapeutic strategy to hamper the growth of malignant plasma cells or to improve the MM-associated bone disease.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Piazza F,Manni S,Semenzato G

doi

10.1016/j.leukres.2012.10.016

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

221-7

issue

2

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(12)00428-6

journal_volume

37

pub_type

杂志文章,评审

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