Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia

Lindsay Nicholson, Thomas Knight, Elizabeth Matheson, Lynne Minto, Marian Case, Maryna Sanichar, Simon Bomken, Josef Vormoor, Andy Hall, Julie Irving

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

14 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)250-256
Aantal pagina's7
TijdschriftGenes Chromosomes and Cancer
Volume51
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - mrt. 2012
Extern gepubliceerdJa

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