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NF kappa B modulators in a model of glucocorticoid resistant, childhood acute lymphoblastic leukemia

Lookup NU author(s): Dr Lindsay Nicholson, Dr Andrew Hall, Dr Chris RedfernORCiD, Professor Julie Irving

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Abstract

Glucocorticoids (GCs) are pivotal agents in the treatment of childhood acute lymphoblastic leukaemia (ALL) but the molecular basis of GC-resistance remains unclear. Expression-array studies have shown that commonly upregulated genes associated with GC-sensitivity include GR, glucocorticoid-induced leucine zipper (GILZ) and I kappa B alpha, which all negatively interact with components of the pro-survival NF kappa B pathway and therefore may be critical determinants of GC-sensitivity. We have investigated these regulators and their effect on NF kappa B activity in GC-resistant descendents of the B-lineage ALL cell line, PreB 697. We show that while differential up regulation of the modulators (GILZ, GR and I kappa B alpha) was demonstrated in GC-sensitive compared to GC-resistant sub-lines, this was not coupled with altered nuclear translocation or functionality of the RelA, p50 or c-Rel subunits of NF kappa B. Thus, GC-resistance in the PreB 697 cell line model is not mediated by NF kappa B, however further investigation of the impact of these GC-sensitive associated proteins on other survival pathways, such as the RAS-RAF-MEK-ERK pathway, is warranted. (C) 2010 Elsevier Ltd. All rights reserved.

Publication metadata

Author(s): Nicholson L, Hall AG, Redfern CP, Irving J

Publication type: Article

Publication status: Published

Journal: Leukemia Research

Year: 2010

Volume: 34

Issue: 10

Pages: 1366-1373

Print publication date: 01/10/2010

ISSN (print): 0145-2126

ISSN (electronic): 1873-5835

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.leukres.2009.12.014

DOI: 10.1016/j.leukres.2009.12.014

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