BRIEF COMMUNICATION A three-way translocation of MLL, MLLT11, and the novel reciprocal partner gene MYO18A in a child with acute myeloid leukemia Marek Ussowicz a, *, Anna Ja  skowiec b , Claus Meyer c , Rolf Marschalek c , Alicja Chybicka a , Tomasz Szczepa  nski d , Olga Haus b,e a Wroclaw Medical University, Department of Pediatric BMT, Hematology and Oncology, Wroclaw, Poland; b Wroclaw Medical University, Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw, Poland; c Institute of Pharmaceutical Biology, Diagnostic Center of Acute Leukemia (DCAL), Goethe-University of Frankfurt, Frankfurt/Main, Germany; d Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland; e Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Genetics, Bydgoszcz, Poland Translocations of the MLL gene are common among neonates and infants with acute lympho- blastic and acute myeloid leukemias. We characterized a new three-way translocation involving MLL in an infant with acute myeloid leukemia who subsequently relapsed and underwent a hema- topoietic stem cell transplant from an unrelated stem cell donor. The translocation was charac- terized using karyotyping and fluorescence in situ hybridization. In this patient, a complex rearrangement fused the distal part of 11q23 with 17q11.2, the distal part of 17q11.2 with 1q21, and the distal part of 1q21 with 11q23, resulting in a three-way translocation; t(1;11;17)(q21;q23;q11.2). The two reciprocal MLL fusion sites were cloned by long-distance inverse polymerase chain reaction, which led to the identification of MLL-MLLT11 and the recip- rocal MYO18A-MLL fusion alleles. Both fusion genes are in-frame and can be translated into functional fusion proteins. Although the MLL-MLLT11 fusion gene has been described in the liter- ature, the reciprocal MYO18A fusion partner is a novel candidate gene in the growing list of recip- rocal MLL fusions. ª 2012 Elsevier Inc. All rights reserved. The MLL gene is located at 11q23 and spans over 100 kb. The coding sequence of this gene consists of 37 exons, with a total length of 11.9 kb, and encodes the MLL protein that contains 3,969 amino acids (1). The post-translational proteolytic cleavage of MLL by TASP1 generates the MLL product N320 and MLL cleavage product C180, which heterodimerize with a non-covalent association (2). The MLL complex helps regulate hemato- poiesis and embryonic development by regulating the expression of the HOX genes (3). The MLL gene is frequently rearranged in acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) and is considered a highly promiscuous oncogene. Over 100 different MLL rearrangements with more than 60 trans- location partner genes (TPGs) have been characterized on the molecular level (4). The highest incidence of MLL gene translocations has been observed in infant leukemias: 60% of AML and 80% of ALL patients (5). The disruption of the MLL gene in leukemia usually occurs in the major breakpoint region (BCR), between exons 8 and 14, which contains topoisomerase II (topo II) consensus sequenceebinding sites that are rich in Alu repetitive elements and poly-A tracts (1,6,7). DNA topo II exposure is associated with MLL trans- location secondary to therapy with topo II-targeting drugs. Whether topo II involvement is direct or indirect is not yet clear (8). Higher-order DNA fragmentation during the initial stages of apoptosis has also been suggested as a mecha- nism that generates MLL translocations (9). The presence of most MLL rearrangements is an unfavorable prognostic factor in various types of leukemias (10). Herein, we describe a novel t(1;11;17) and unique MYO18A-MLL fusion in a patient with AML. Received September 13, 2011; received in revised form February 14, 2012; accepted February 15, 2012. * Corresponding author. E-mail address: ussowicz@tlen.pl 2210-7762/$ - see front matter ª 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergen.2012.02.006 Cancer Genetics 205 (2012) 261e265