Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with...

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Detalles Bibliográficos
Autores principales: Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C., McCastlain, Kelly, Reshmi, Shalini C., Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L., Mungall, Andrew J., Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M., Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E., Maloney, Kelly, Mattano Jr, Leonard A., Angiolillo, Anne, Salzer, Wanda L., Burke, Michael J., Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P., Minden, Mark D., Moorman, Anthony V., Patel, Bella, Fielding, Adele K., Rowe, Jacob M., Luger, Selina M., Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J., Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D., Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M., Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L., L. Loh, Mignon, P. Hunger, Stephen, Mullighan, Charles G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105166/
https://www.ncbi.nlm.nih.gov/pubmed/27824051
http://dx.doi.org/10.1038/ncomms13331
Descripción
Sumario:Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.

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