t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the HMGA2 gene

Polycythemia vera (PV) is a chronic myeloproliferative disorder (MPD) characterized by an excess production of apparently normal erythrocytes and a variable overproduction of leukocytes and platelets in the absence of a defined cause. Recent PV studies have identified in several patients an acquired valine-tophenylalanine mutation at amino acid 617 (V617F) in the Janus kinase 2 (JAK2) tyrosine kinase gene. This mutation, however, is not present in all PV patients.1,2 Other studies have reported a number of gene fusions resulting from chromosomal aberrations, but no recurrent chromosomal abnormality has been identified so far. We report here a PV case showing a novel, balanced t(3;12)(q26;q14) translocation, involving the 30 UTR of the gene HMGA2 (high mobility group AT-hook 2 isoform a) and the coding region of the TNIK (Traf2- and Nck-interacting kinase). Molecular analyses demonstrated an overexpression of HMGA2, which, however, was not due to the formation of a fusion transcript with TNIK, but, very likely, to a position effect. TNIK expression pattern was not affected by the rearrangement.