Experimental Oncology 27, 71-75, 2005 (March) 71 Exp Oncol 2005 27, 1, 71-75 The MLL gene, also called HRX or ALL-1, was orig- inally identified by its involvement in recurrent chromo- somal translocations in acute lymphocytic leukemia and acute myelogenous leukemia (AML) in 1991. It repre- sents the human homolog of the Drosophila trithorax gene whose function is required for proper homeotic gene expression and regulation of chromatin structure. MLL acts as a transcription factor and can regulate tar- get genes that are involved in cell growth and prolifer- ation. The MLL gene, located at cytogenetic band 11q23, has been reported to fuse with more than 50 different translocation partner genes, many of which have been cloned [1]. In all cases studied thus far, the chromosome 11 breakpoints have been clustered within a 9-kb region spanning exons 5–11 of MLL. The trans- locations result in an in-frame 5′MLL/3′ partner-gene transcript resulting from the joining of the amino-termi- nal part of MLL to the carboxyl end of the partner prod- uct, creating fusion proteins that are critical for leuke- mogenesis [2, 3]. A high partner diversity favors the hypothesis that the MLL disturbance by itself is suffi- cient for disruption of normal hematopoietic differenti- ation. AML with 11q23/ MLL rearrangement involving MLL GENE ALTERATIONS IN RADIATION-ASSOCIATED ACUTE MYELOID LEUKEMIA Sergiy V. Klymenko 1, *, Karin Bink 2 , Klaus R. Trott 3 , Vladimir G. Bebeshko 1 , Dimitry A. Bazyka 1 , Iryna V. Dmytrenko 1 , Iryna V. Abramenko 1 , Nadia I. Bilous 1 , Horst Zitzelsberger 4 , Andrei V. Misurin 5 , Michael J. Atkinson 2 , Michael Rosemann 2 1 Research Centre for Radiation Medicine, Academy of Medical Science of Ukraine, Kyiv 04050, Ukraine 2 Institute of Pathology, National Research Center for Environment and Health, Neuherberg 85764, Germany 3 Gray Cancer Institute, Northwood Middlesex HA6 2JR, United Kingdom 4 Institute of Molecular Biology, National Research Center for Environment and Health, Neuherberg 85764, Germany 5 Hematology Research Centre, 125167 Moskow, Russia Aim: Although acute myelogenous leukemia (AML) arising after radiation exposure is considered to be secondary, little is known about the molecular mechanisms by which the radiation induces the leukemogenic phenotype. The aim of the study was to analyze whether the MLL translocations are as frequent in radiation-associated AML as in spontaneous AML cases. Methods: Sixty one AML samples obtained at diagnosis were analyzed for the presence of MLL abnormalities using fluorescent in situ hybridization and/or reverse transcription polymerase chain reaction. Of these patients, 27 had experienced radiation exposure due to the Chernobyl accident, 32 were non-irradiated (spon- taneous AML), and 2 developed therapy-related AML after chemotherapy with topoisomerase II inhibitors. Results: MLL gene translocations were detected in both groups of spontaneous and therapy-related AML (1/32 and 1/2 cases respectively). The sole MLL rearrangement found in the group of radiation-associated AML patients was a duplica- tion of the gene. Conclusion: Our data preclude the involvement of MLL gene translocations in radiation-induced leukemogenesis, but support the assumption that loss and gain of chromosomal material could be crucial in the leukemogenesis of AML patients with the history of radiation exposure due to the Chernobyl accident. Key Words: acute myelogenous leukemia, ionizing radiation, Chernobyl accident, MLL, translocation, duplication. Received: January 10, 2005. *Correspondence: Fax: (044) 451 8294 E-mail: klymenko_sergiy@yahoo.co.uk Abbreviations used: AML — acute myelogenous leukemia; FISH — fluorescence in situ hybridization; RT-PCR — reverse transcription polymerase chain reaction. different partner genes seems to comprise a biologi- cally and clinically homogeneous entity despite the large variety of different fusion partner genes. Overall sur- vival is short and is comparable to AML with an unfa- vorable karyotype [4]. The detection and characterization of chromosom- al rearrangements in AML has provided the means to identify distinct biologic and prognostic subgroups and to establish a WHO pathogenesis-oriented classifica- tion of the disease [5]. MLL abnormalities are being observed both in de novo and secondary AML cases. AML patients with MLL abnormalities but without a doc- umented exposure to therapeutic, occupational or en- vironmental genotoxins prior to the onset of the dis- ease are considered as de novo or spontaneous cas- es, although these terms are not completely appropriate. The other category of AML patients with MLL abnor- malities represents secondary cases related to thera- py with agents that bind to and inhibit DNA-topo- isomerase II. Secondary AML after treatment with to- poisomerase II inhibitors are well characterized and usually present with overt leukemia without a myelo- dysplastic phase, have a short latency period (6– 36 months), and a relatively favorable response to che- motherapy [6–14]. Although AML developing after radiation exposure are also considered to be secondary, little is known about the molecular mechanisms by which the radia- tion induces the acute leukemogenic phenotype. There