t(3;21)(q22;q22) leading to truncation of the RYK gene in atypical chronic myeloid leukemia Francesca Micci a, * , Ioannis Panagopoulos b , Lisbeth Haugom a , Hege Kilen Andersen a , Geir E. Tjønnfjord c,d , Klaus Beiske e , Sverre Heim a,d a Department of Medical Genetics, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway b Department of Clinical Genetics, University Hospital, Lund, Sweden c Medical Department, Division of Hematology, Rikshospitalet University Hospital, Oslo, Norway d Faculty of Medicine, University of Oslo, Oslo, Norway e Department of Pathology, Rikshospitalet University Hospital, Oslo, Norway article info Article history: Received 14 October 2008 Received in revised form 24 November 2008 Accepted 8 December 2008 Keywords: Fusion gene Karyotyping RYK ATP5O aCML abstract The analysis of a small number of patients with atypical chronic myeloid leukemia showing balanced chromosomal translocations has revealed diverse tyrosine kinase fusion genes, most commonly involving FGFR1, PDGFRA, PDGFRB, JAK2, and ABL. We present a case of aCML with a 3q22;21q22-translocation that led to truncation of the receptor-like tyrosine kinase (RYK) gene and its juxtaposition with sequences from chromosome 21 including the ATP5O gene coding for a mitochondrial ATP synthase. The resulting fusion was not in frame, however, which is why we speculate that an abrogated RYK gene product rather than a chi- meric protein might be the leukemogenic result. Ó 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Atypical chronic myeloid leukemia (aCML) demon- strates myelodysplastic as well as myeloproliferative fea- tures at the time of diagnosis. The disease is characterized by principal involvement of the neutrophil series with leukocytosis comprising immature as well as mature dysplastic neutrophil granulocytes. Multilineage dysplasia is common, reflecting the stem cell origin of aCML. As another defining feature, the neoplastic cells do not harbor a Philadelphia (Ph) chromosome with the resulting BCR/ABL1 fusion gene [1]. The relative incidence of aCML is reported to be 1–2 cases for every 100 cases of Ph + BCR/ABL1 + CML [2]. The Mitelman database of chromosome aberrations in cancer [3] presently lists 51 aCML cases with an abnormal karyotype. Although cytogenetic abnormalities, including +8 and +21, have been described in up to 80% of patients with aCML, the aberration pattern has shown none of the specificity typical of CML [4–8]. Recently, however, fusion genes were repeatedly described in aCML. Reiter et al. [9] and Bousquet et al. [10] simultaneously identified a PCM1/JAK2 in seven aCML patients carrying a t(8;9)(p22;p24), and also an H4/PDGFbR fusion has been re- ported in a few cases of aCML carrying a t(5;10)(q33;q22) [11–13]. Both these translocations target tyrosine kinases, perhaps hinting at a general pathogenetic mechanism in this disease. We report a new case of aCML with a 3;21-translocation leading to fusion of the receptor-like tyrosine kinase (RYK) gene from 3q22 with sequences from chromosome 21 including the mitochondrial ATP synthase (ATP5O) gene from 21q22. Since the resulting fusion was not in frame, we speculate that truncation of RYK was the central path- ogenetic outcome of the translocation. 0304-3835/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.canlet.2008.12.016 * Corresponding author. Tel.: +47 22934436; fax: +47 22935477. E-mail address: francesca.micci@labmed.uio.no (F. Micci). Cancer Letters 277 (2009) 205–211 Contents lists available at ScienceDirect Cancer Letters journal homepage: www.elsevier.com/locate/canlet