NUP98 Rearrangement in Acute Myelomonocytic Leukemia With t(11;19)(p15;p12): The First Case Report Worldwide

Dear Editor, AML is a group of heterogeneous diseases derived from various cytogenetic and molecular abnormalities that are significant for diagnosis, treatment, and prognosis in many cases. We report a rare case of AML harboring t(11;19)(p15;p12) that was detected with whole-genome sequencing (WGS). A 33-yr-old woman was admitted to a local hospital with abdominal pain and diarrhea for five days. After conservative treatment, the symptoms improved. However, definite leukocytosis persisted; therefore, the patient visited our hospital for further evaluation. The initial complete blood count showed an Hb level of 7.6 g/dL, white blood cell (WBC) count of 29.48×10/L, and platelet count of 53×10/L. On the peripheral blood smear, differential counts revealed 15% segmented neutrophils, 16% lymphocytes, 60% monocytes, 1% eosinophils, 1% atypical lymphocytes, 1% promyelocytes, 6% blasts, and 4 nucleated red blood cells (RBCs) per 100 WBCs. RBCs were macrocytic and hyperchromic with mild polychromasia and anisocytosis. The bone marrow (BM) aspirate smear showed increased myeloblasts and monoblasts (7.6% and 42.0% of all nucleated cells, respectively) (Fig. 1A). Some blasts were positive for myeloperoxidase (MPO), Sudan black B, specific esterase, and non-specific esterase stains, and showed fine granular positivity for periodic acid-Schiff stain. BM biopsy revealed a markedly hypercellular marrow (95–100% cellularity) with infiltrations of leukemic blasts. Flow cytometric analysis revealed the blasts to be positive for CD11c, CD14, CD33, CD64, CD71, MPO, and HLA-DR, which indicated acute leukemia of the myeloid lineage with a monocytic component. Chromosomal analysis of the BM specimen showed 46,XX,t(11;19)(p15;p12)[26]/46,XX[1] (Fig. 1B). FISH analysis showed normal genotypes for AML1-ETO, PML-RARα, CBFB, and MLL. In the real-time allele-specific PCR assay for FLT3 mutations, a D835Y mutation was detected. Multiplex reverse transcriptase PCR using Hemavision kit (DNA Technology, Aarhus, Denmark) did not detect any other mutations. For further evaluation, we sent the BM samples out for WGS and RNA sequencing (RNA-seq) analysis. The WGS analysis was performed by using the HiSeq X Ten system (Illumina, San Diego, CA, USA), and RNA-seq analysis was performed by using the 100-bp paired-end mode of the TruSeq Rapid PE Cluster kit and the TruSeq Rapid SBS kit (Illumina, San Diego, CA, USA). The WGS analysis revealed the presence of 16 in-frame gene fusions, including a fusion between NUP98 and ZNF91 (Fig. 2A). To clarify these findings, additional FISH analyses using the NUP98 break-apart FISH probe kit (Empire Genomics,