Biclonal and biallelic deletions occur in 20% of B-ALL cases with IKZF1 mutations

Autor:	Bernard Drenou, Raoul Herbrecht, Michèle Legrain, Arnaud Dupuis, Pierre G. Lutz, Susan Chan, Laurent Mauvieux, Philippe Kastner, Marie-Pierre Gaub
Rok vydání:	2012
Předmět:	Gene isoform Genetics Cancer Research Mutation Hematology Biology medicine.disease_cause medicine.disease Molecular biology Ikaros Transcription Factor Exon Leukemia Oncology medicine Haploinsufficiency Gene Loss function
Zdroj:	Leukemia. 27:503-507
ISSN:	1476-5551 0887-6924
Popis:	The IKZF1 gene encodes the Ikaros transcription factor, a key regulator of lymphocyte differentiation.1 IKZF1 is mutated in 20–30% of B-cell acute lymphoblastic leukemia (B-ALL) mostly by genomic deletions.2, 3, 4 Several reports have shown that IKZF1 deletions are associated with an adverse prognosis, especially in pediatric patients.3, 4, 5, 6, 7, 8, 9, 10 Ikaros mutations fall mainly into three types: (a) deletions of exons 4–7 (Δ4–7), which lead to the synthesis of the Ikaros-6 (Ik6) dominant-negative isoform; (b) deletions of exons 2–7 (Δ2–7), which delete the initiation codon and lead to haploinsufficiency; and (c) larger deletions of various sizes, which affect the coding exons (referred to below as ‘complete’ deletions). Thus, IKZF1 mutations have until now been separated into dominant-negative and haploinsufficient groups. Here we report that about 20% of B-ALL patients with IKZF1 mutations present two distinct deletions. These deletions are biallelic, leading to a complete loss of Ikaros function, or biclonal, marking distinct clones within the leukemia. These results highlight a more complex picture of IKZF1 loss of function in B-ALL than thought previously.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6358224c609e8a88c832a6a11b70db47 https://doi.org/10.1038/leu.2012.204 Zobrazit plný text záznamu