Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome

Blood
Blaine W RobinsonC A Felix

Abstract

We prospectively observed a child exposed to intensive multimodality therapy for metastatic neuroblastoma from emergence of a MLL translocation to disease diagnosis. The t(4;11)(p12;q23) was detected in the marrow 17 months after starting treatment following topoisomerase II poisons, alkylating agents, local radiation, hematopoietic stem cell transplantation, anti-GD2 monoclonal antibody with granulocyte macrophage-colony-stimulating factor, and a high cumulative dose of oral etoposide. Reciprocal genomic breakpoint junctions and fusion transcripts joined MLL with FRYL, the Drosophila melanogaster protein homologue of which regulates cell fate. Etoposide metabolites induced topoisomerase II cleavage complexes that could form both breakpoint junctions. Cells harboring the translocation replaced the marrow without clinical evidence of leukemia and differentiation appeared unaffected for 37 months. Subsequent bilineage dysplasia and increased blasts in addition to the translocation fulfilled criteria for MDS. The MEIS1 target gene of typical MLL fusion oncoproteins was underexpressed before and at MDS diagnosis. These results are consistent with repair of topoisomerase II cleavage from etoposide metabolites as the translocation me...Continue Reading

References

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Citations

Mar 29, 2014·Phytochemistry Reviews : Proceedings of the Phytochemical Society of Europe·Adam C Ketron, Neil Osheroff
May 12, 2009·Pediatric Blood & Cancer·Carolyn A Felix
Oct 22, 2008·Genes, Chromosomes & Cancer·Jan ZunaJan Trka
Feb 6, 2014·Annals of the New York Academy of Sciences·Maryjean PendletonNeil Osheroff
Aug 23, 2008·Genes, Chromosomes & Cancer·Nathalie A JohnsonDouglas E Horsman

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