Cancer Genetics and Cytogenetics 122 (2000) 79–82 0165-4608/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0165-4608(00)00293-4 Translocation (2;8)(p12;q24) associated with a cryptic t(12;21)(p13;q22) TEL/AML1 gene rearrangement in a child with acute lymphoblastic leukemia Mignon L. Loh a,b,c , Yvan Samson d , Elizabeth Motte a , Lisa A. Moreau e , Virginia Dalton b , Stacy Waters b , Stephen E. Sallan b , D. Gary Gilliland a,e, * a Division of Hematology-Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA b Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children’s Hospital, Boston, Harvard Medical School, Boston, MA 02115, USA c Current address: Division of Pediatric Hematology-Oncology, University of California, San Francisco, San Francisco, CA 94143, USA d Laval University Hospital, Quebec, Canada e Department of Cytogenetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA Received 16 September 1999; received in revised form 26 May 2000; accepted 30 May 2000 Abstract We report a case of childhood acute lymphoblastic leukemia with the simultaneous occurrence of a t(2;8)(p12;q24) typically associated with mature B cell or Burkitt leukemia, and a t(12;21)(p13; q22) exclusively associated with pre-B cell ALL. The lymphoblasts were characterized as L2 mor- phology by the French–American–British classification. However, there were atypical morpho- logic findings for L2 ALL, including vacuolization in some cells. The lymphoblasts were periodic acid-Schiff positive and myeloperoxidase negative. Immunophenotypic analysis revealed that the majority of lymphoblasts were TdT+, CD10+, CD19+, CD20-, and cytoplasmic +. These fea- tures were consistent with an immature pre-B cell leukemia phenotype with some characteristics of a mature B-cell leukemia. A t(2;8)(p12;q24)(p12;q24), characteristic of mature B-cell leukemia or Burkitt type leukemia, was detected by conventional cytogenetics with no other cytogenetic ab- normalities. However, diagnostic peripheral blood and bone marrow specimens demonstrated si- multaneous occurrence of a cryptic t(12;21)(p13;q22) by both FISH and RT-PCR. The simulta- neous occurrence of these translocations in a pediatric patient have implications for the pathogenesis of leukemias with t(2;8)(p12;q24) as well as t(12;21)(p12;q22). Analysis of additional cases of leu- kemia with translocations involving the MYC locus on 8q24 will be required to determine the fre- quency of association with the cryptic t(12;21)(p13;22), and the prognostic significance of the si- multaneous occurrence of the translocations. © 2000 Elsevier Science Inc. All rights reserved. 1. Introduction The diagnosis of leukemic subtypes has been enhanced through the use of increasingly sophisticated methods of analysis. In addition to morphology and cytochemical stains such as periodic acid-Schiff or myeloperoxidase, flow cy- tometry and conventional cytogenetics are standard tests used to classify subsets of acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). In recent years, fluorescence in situ hybridization (FISH) and re- verse-transcriptase polymerase chain reaction (RT-PCR) techniques have been added to the roster of diagnostic tests that more accurately identify chromosomal translocations in a variety of leukemias, including those that are not detect- able by conventional cytogenetics. The most frequent exam- ple of such a cryptic translocation is the product of the t(12; 21)(p13;q22)(p13;q22), which fuses the pointed domain of the TEL gene with nearly the entire coding sequence of the AML1 gene [1,2], also known as CBFA2 or RUNX1. A less frequent, cytogenetically evident translocation associated with mature B-cell leukemia, is the t(2;8)(p12;q24), which places the C-MYC proto-oncogene on 8q24 in close proxim- ity to the immunoglobulin  light chain promoter at 2p12. We report a case of the simultaneous occurrence of the TEL/AML1 fusion with t(2;8)(p12;q24) in a child with ALL. The implications of these simultaneous cytogenetic abnormalities in pathogenesis and therapy are discussed. * Corresponding author. Tel: 617-525-5525; fax: 617-525-5530. E-mail address: gilliland@calvin.bwh.harvard.edu (G. Gilliland).