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Mismatch repair and the downstream target genes, PAX5 and Ikaros, in childhood acute lymphoblastic leukemia

Lookup NU author(s): Elizabeth Matheson, Lynne Minto, Emeritus Professor Andy Hall, Professor Julie Irving

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Abstract

The mismatch repair (MMR) pathway is a post-replicative DNA repair process and MMR deficiency is a common feature of ALL cell lines. In this study we have investigated MMR deficiency in a large cohort of primary relapsed ALL (n = 40) and investigated coding microsatellites (MS) of the lymphoid transcription factors, PAX5 and IKZF1 as downstream target genes. Only one patient showed MMR deficiency, as evidenced by microsatellite instability, which was acquired at relapse and was associated with reduced expression of both MLH1 and MSH2. Coding MS in candidate target genes including PAX5, IKZF1, BAX and TGFBRII were all wild type in this patient but the MMR-deficient cell line REH, was confirmed to have a coding MS in both PAX5 and TGFBRII. Whilst MMR deficiency is not highly prevalent in primary ALL, optimisation of the drug regimen to omit/replace thioguanines should be considered for children with MMR deficiency and/or reduced expression of key pathway components. (C) 2010 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Best A, Matheson E, Minto L, Hall AG, Irving JAE

Publication type: Article

Publication status: Published

Journal: Leukemia Research

Year: 2010

Volume: 34

Issue: 8

Pages: 1098-1102

Print publication date: 01/08/2010

ISSN (print): 0145-2126

ISSN (electronic): 1873-5835

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.leukres.2010.02.017

DOI: 10.1016/j.leukres.2010.02.017


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