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Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia

Lookup NU author(s): Dr Lindsay Nicholson, Elizabeth Matheson, Lynne Minto, Marian Case, Maryna Sanichar, Dr Simon BomkenORCiD, Professor Hermann Josef Vormoor, Dr Andrew Hall, Professor Julie Irving


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Casitas B-lineage lymphoma (CBL) proteins are RING finger ubiquitin E3 ligases that attenuate the signaling of receptor tyrosine kinases and are mutated in a number of myeloid disorders. In this study, mutational screening of the linker-RING domains of CBL and CBLB was performed by denaturing high performance liquid chromatography in a cohort of diagnostic (n = 180) or relapse (n = 46) samples from children with acute lymphoblastic leukemia. Somatic mutations were identified in three children, giving an overall incidence of 1.7% and involved small deletions affecting the intron/exon boundaries of exon 8, leading to skipping of exon 8 and abolishing E3 ligase function. Mutated primary samples were associated with constitutive activation of the RAS pathway and sensitivity to MEK inhibitors was shown. Thus, mutation of CBL is an alternative route to activate the RAS pathway and may identify children who are candidates for MEK inhibitor clinical trials. (c) 2011 Wiley Periodicals, Inc.

Publication metadata

Author(s): Nicholson L, Knight T, Matheson E, Minto L, Case M, Sanichar M, Bomken S, Vormoor J, Hall A, Irving J

Publication type: Article

Publication status: Published

Journal: Genes, Chromosomes & Cancer

Year: 2012

Volume: 51

Issue: 3

Pages: 250-256

Print publication date: 10/11/2011

ISSN (print): 1045-2257

ISSN (electronic): 1098-2264

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/gcc.20949


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