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. 2021 Jan 24;10(2):225. doi: 10.3390/cells10020225

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Integrin-dependent activation of GSK3β and leukemic stem cell resistance. Adhesion of leukemic stem cells to fibronectin or to osteoblasts triggers the formation of a molecular complex around the adaptor protein RACK1 associated to the cytoplasmic domain of integrin. In this molecular complex, GSK3β is activated through its de-phosphorylation by the phosphatase PP2A. Thus, leukemic stem cell resistance to cytotoxic stress is promoted by different mechanisms, among them NF-kB activation. Of note, the dependence of hematopoietic stem cells to GSK3β displays a sexual dimorphism that is switched upon leukemogenesis.