The First Korean Case of Childhood Acute Myeloid Leukemia with Inv(11)(p15q22)/NUP98-DDX10 Rearrangement: A Rare but Recurrent Genetic Abnormality

Inv(11)(p15q22)/NUP98-DDX10 rearrangement is a rare but recurrent chromosomal translocation associated with myeloid malignancies. Structural chromosomal rearrangements of the nucleoporin 98 gene (NUP98) at 11p15.4 produce NUP98 fusions with the DDX10 DEAD (Asp-Glu-Ala-Asp) box polypeptide 10 (DDX10) gene on chromosome 11q22 [1]. To date, only 15 such cases, except the present case, with de novo or therapyrelated myeloid disorders have been reported [1-8]. Three NUP98-DDX10 fusion isoforms, types I, II, and III, have been reported. The type I fusion, which fuses NUP98 exon 12 (NM_139131.1) with DDX10 exon 6 (NM_004398.2), has been reported in 2 adult therapy-related AML patients [1, 8]. The type II fusion, which fuses NUP98 exon 14 with DDX10 exon 7, has been reported in 12 cases. The type III fusion, which fuses NUP98 exon 15 and DDX10 exon 7, has been reported in 1 adult de novo AML patient with a concurrent case of type II fusion [7]. Herein we report a de novo childhood AML patient with inv(11)(p15q22)/NUP98-DDX10 rearrangement for the first time in Korea. A 4-yr-old boy presented with petechiae and easy bruising. His complete blood count revealed the following: Hb, 7.7 g/dL; leukocyte count, 7.64×10/L (absolute neutrophil count, 0.32 ×10/L); and platelets, 42×10/L. Additional analysis of the peripheral blood revealed 15% myeloblasts and leukoerythroblastic features. The bone marrow (BM) study showed 55% blasts with dysplastic erythropoiesis and megakaryopoiesis, suggesting AML with myelodysplasia-related changes. The estimated cellularity of the BM section was variable at 10-100% (overall 50%). Flow cytometry revealed that the blasts were positive for CD13, CD33, CD64, CD11c, CD117, cMPO, HLA-DR, and CD34 (CD64 and CD34 were weakly expressed). Chromosomal analysis performed on a short-term culture of BM cells using the Giemsa banding technique revealed that the patient’s karyotype was 46,XY,inv(11)(p15q22)[19]/46,XY[1] (Fig. 1). FISH analysis with probes for EGR1 (5q-), D7S522 (7q-), TP53/CEP17 [i(17q)/ t(17p)], and MLL [t(11q23)] (Vysis, Downers Grove, IL, USA) showed no cytogenetic abnormalities. The HemaVision (DNA Technology, Aarhus, Denmark) screen was negative for all detectable fusion transcripts. Mutation analyses for NPM1 and internal tandem duplications of FLT3 and CEBPA were negative. One microgram of total RNA was reverse transcribed for reverse transcription (RT)-PCR experiments for further evaluation of cytogenetic abnormalities. The NUP98-DDX10 fusion transcript was detected by using previously described primers [1], and