1. NUP98is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis
- Author
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Struski, S, Lagarde, S, Bories, P, Puiseux, C, Prade, N, Cuccuini, W, Pages, M-P, Bidet, A, Gervais, C, Lafage-Pochitaloff, M, Roche-Lestienne, C, Barin, C, Penther, D, Nadal, N, Radford-Weiss, I, Collonge-Rame, M-A, Gaillard, B, Mugneret, F, Lefebvre, C, Bart-Delabesse, E, Petit, A, Leverger, G, Broccardo, C, Luquet, I, Pasquet, M, and Delabesse, E
- Abstract
Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98(NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11fusion gene (4.0%). The most frequent NUP98fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3ITD, WT1, CEBPA, NBPF14, BCRand ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.
- Published
- 2017
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