CASE REPORT Complex t(8;13;21)(q22;q14;q22)eA Novel Variant of t(8;21) in a Patient with Acute Myeloid Leukemia (AMLeM2) Achandira Muthappa Udayakumar, a Salam Alkindi, b Anil Vasanth Pathare, b and John Alexander Raeburn a a Department of Genetics, College of Medicine and Health Sciences, and b Department of Haematology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman Received for publication May 16, 2007; accepted July 31, 2007 (ARCMED-D-07-00208). Variants of the t(8;21)(q22;q22) involving chromosome 8, 21, and other chromosomes ac- count for about 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. We report a case of AMLM2 with t(8;13;21)(q22;q14;q22), not reported earlier. Using a dual-color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrate an ETO/AML1 fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosomes 8 and 13, to demon- strate the three-way translocation t(8;13;21)(q22;q14;q22). Involvement of chromosome region 13q14 has never been reported earlier, although region 13q12 as a variant in AML with t(8;21) has been reported earlier. The possible role of genes in this region in leuke- mogenesis, its response to the treatment and its clinical implications are dis- cussed. Ó 2008 IMSS. Published by Elsevier Inc. Key Words: Variant translocation, Leukemia, Acute myeloid leukemia, Karyotype. Introduction Acute myeloid leukemia (AML) is well characterized by spe- cific chromosomal aberrations that correspond to various subtypes based on French-American-British (FAB) classifi- cation of acute leukemia. Translocation (8;21)(q22;q22) is a frequent non-random cytogenetic anomaly in AML and is strongly associated with FAB subtype M2 (AMLeM2). It oc- curs in |10e15% of AML patients, whereas O90% of t(8;21)-positive leukemias have FAB AMLeM2 morphol- ogy (1) and is an independent entity according to the World Health Organization (WHO) classification (2). At the molecular level, the two genes involved in t(8;21) are AML1 at 21q22 and ETO at 8q22 (3,4). AML1 gene fuses to the ETO gene in generating a chimeric AML1/ ETO fusion gene on the der(8). AML1 and ETO are both involved in transcriptional regulation of genes in the hematopoietic precursor cells. In the overall majority of cases, the AML1/ETO fusion gene is the result of a balanced translocation between chromosomes 8 and 21 (5). In approximately 3% of AML patients, t(8;21) occurs as a complex variant involving chromosomes 8 and 21 and a third or fourth chromosome (6). Patients with these vari- ants show typical features of t(8;21) AML morphologically, and in a limited number of patients studied the AML1/ETO fusion transcripts detected were similar to those of t(8;21) (3,4). We report here a female patient with AML (FABe M2) showing a complex t(8;13;21) involving a new break- point 13q14, which has previously not been reported in the literature. Case Report NSNR, a 33-year-old Omani female, was referred with a history of anorexia for 5 weeks and fever during 3 weeks. She was referred due to anemia, pancytopenia, and abnor- mal blood smear. There was no significant past medical his- tory. On examination the patient looked pale, overweight, and with few ecchymotic skin lesions. There was no Published previously online November 15, 2007. Conflict of Interest: None Address reprint requests to: Dr. A.M. Udayakumar, Cytogenetics Lab- oratory, Department of Genetics, College of Medicine and Health Sci- ences, P.B. 35, P.C. 123, Sultan Qaboos University, Muscat, Sultanate of Oman; E-mail: amuk19@hotmail.com or udaya@squ.edu.Om 0188-4409/08 $esee front matter. Copyright Ó 2008 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2007.09.002 Archives of Medical Research 39 (2008) 252e256