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Título:	Genomic and transcriptomic landscape of t(4;11)(q21q24)/MLL-AF4+ Infant pro-B acute lymphoblastic leukemia
Autor:	Agraz-Doblas, Antonio; Varela, Ignacio CSIC ORCID; Menéndez, Pablo
Fecha de publicación:	2017
Citación:	XL SEBBM Congress (2017)
Resumen:	Infant pre/pro B-cell Acute Lymphoblastic Leukemia (B-ALL) is the most common pediatric cancer, representing the 25% of all malignant tumors in childhood, especially when harboring MLL-gene rearrangements. A particular subtype of B-ALL characterized by the genomic translocation t(4;11)(q21q24) which fuses the MLL with AF4 is frequently found in newborns/infants and is associated with dismal prognosis [Pui et al., 2011]. MLLr are unique clonal leukemogenic drivers which initiate leukemia without additional genetic lesions [Dobbins et al., 2013, Andersson et al., 2015]. Here, we have performed a high-coverage (110X) exome sequencing, whole-exome and RNAseq in a cohort of 42 infants B-ALLs (27 MLL-AF4+, 5 MLL-AF9 and 10 non-MLL). An independent cohort of 43 MLL-AF4+, 11 MLL-AF9+, and 28 non-MLL B-ALL was used for validation. Our results show a slight higher mutation load than previously described, revealing a predominant leukemic clone carrying a mean of 2 non-silent mutations and the presence of some somatic mutations in minor tumor subclones. Recurrent mutations were found in KRAS and NRAS, with a higher frecuency of NRAS mutations in MLL-AF4+ (42%) than in the other groups. Interestingly, our results also show an accumulation of a higher number of mutations in relapse without RAS participation, which could indicate that these mutations do not off er selective advantage in that context. In addition, RNAseq studies have revealed new genes/pathways diff erentially expressed in this leukemia which could play an important role in the development of the disease. Taken together, our results confi rm an extremely low mutation rate in infant MLL-AF4+ B-ALL, and suggest that the target cell of origin and epigenetic portraits may be crucial in the pathogenesis of this dismal leukemia.
Descripción:	Resumen del póster presentado al XL Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Barcelona del 23 al 26 de octubre de 2017.-- Agraz-Doblas, Antonio et al.
URI:	http://hdl.handle.net/10261/164866
Aparece en las colecciones:	(IBBTEC) Comunicaciones congresos