Translocation t(6;9)(p22;q34)/DEK-NUP214 rearranged Pediatric AML: A Retrospective International Study

• Published in: Blood 2012-11, Vol.120 (21), p.538-538
• Main Authors: Sandahl, Julie Damgaard, Coenen, Eva A., Forestier, Erik, Harbott, Jochen, Johansson, Bertil, Kerndrup, Gitte, Adachi, Souichi, Auvrignon, Anne, Beverloo, H. Berna, Chilton, Lucy, de Haas, Valerie, Harrison, Christine J, Inaba, Hiroto, Kaspers, Gertjan J.L., Liang, Der-Cherng, Lin, Kuo-Sin, Masetti, Riccardo, Perot, Christine, Pession, Andrea, Raimondi, Susana C., Reinhardt, Katarina, Tomizawa, Daisuke, von Neuhoff, Nils, Zecca, Marco, van den Heuvel-Eibrink, Marry M., Hasle, Henrik
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.538.538

Abstract 538 The cytogenetic subgroup t(6;9)(p22;q34), previously often reported as a breakpoint in 6p23, is defined as a distinct entity in the 2008 WHO classification of acute myeloid leukemia (AML). The translocation results in a chimeric fusion between DEK at 6p22.3 and NUP214 at 9q34.13 generating the DEK-NUP214 fusion gene. In adults, t(6;9) is associated with young age, very poor outcome, and a higher prevalence of FLT3-ITD than in any other type of AML. To date, the clinical impact of t(6;9) has not been independently described in a pediatric cohort. In this retrospective study, we aimed to characterize the clinical, genetic and morphological features of t(6;9) in childhood AML and to evaluate outcome. Children aged 0–18 years and diagnosed with t(6;9)-positive AML or MDS within the period January 1, 1993 to December 31, 2011 were included. The presence of the translocation was determined by conventional karyotyping, FISH, or RT-PCR. Patients with Down syndrome and therapy-related AML were excluded. All major pediatric AML study groups were invited to submit clinical data. In addition, diagnostic smears and biopsies were requested for central reviewing and viable cells or RNA for gene expression profiling (GEP). All karyotypes were centrally reviewed and described according to the International System for Human Cytogenetic Nomenclature. GEP was performed on available frozen diagnostic samples from 297 pediatric AML patients including 6 patients with t(6;9). Based on p-value, log-fold change and biological relevance, the following 4 genes were selected for validation by quantitative real-time PCR (RT-qPCR); eyes absent homolog 3 at 1p35.3 (EYA3), sestrin 1 at 6q21(SESN1), PR domain containing 2, with ZNF domain at 1p36.21 (PRDM2, also known as RIZ1), and histone cluster 2, H4a at 1q21.2 (HIST2H4). Validation was performed on 48 patient samples: t(6;9) (n=17), other pediatric AML (n=31) and 14 cell lines including one with t(6;9)(p22;q34). A total of 58 pediatric patients with a DEK-NUP214 t(6;9) myeloid malignancy from 24 study groups were included in the study: 50 were diagnosed as de novo AML (0.5% of all AML during the study period) and 8 as MDS. Patients with t(6;9) were characterized by a late onset as well as male preponderance; median age was 11 years (range 3–18 years) and the male:female ratio 39:19 (p