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Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia
Author(s) -
Nicholson Lindsay,
Knight Thomas,
Matheson Elizabeth,
Minto Lynne,
Case Marian,
Sanichar Maryna,
Bomken Simon,
Vormoor Josef,
Hall Andy,
Irving Julie
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20949
Subject(s) - lymphoblastic leukemia , cancer research , lymphoblastic lymphoma , lymphoma , medicine , oncology , leukemia , immunology , t cell , immune system
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. © 2011 Wiley Periodicals, Inc.