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The t(10;11)(p13;q14-21) is a non-random translocation described in acute lymphoblastic and myeloid leukaemias. It results in the fusion of the gene CALM, which encodes a clathrin assembly protein, on 11q14 to the gene AF10, a putative transcription factor on 10p13. Here we describe for the first time, the occurrence of a CALM-AF10 fusion in a case of acute megakaryoblastic leukaemia. Fluorescence in situ hybridisation and reverse transcriptase polymerase chain reaction were used to confirm the presence of a CALM-AF10 fusion. A novel splice variant of CALM missing nt 1927-2091 was also detected. Though CALM is a cytoplasmic protein, the chimaeric fusion product is able to localise to both the nucleus and cytoplasm. Analysis of the fusion variants suggests, however, that the critical fusion product is likely to be cytoplasmic and contain the interactive leucine zipper of AF10. [ABSTRACT FROM AUTHOR]

Chimaeric fusion genes created by nonrandom chromosomal translocations are characteristic of childhood acute lymphoblastic (ALL) and myeloid (AML) leukaemias. Although the mechanisms leading to these chromosomal rearrangements are unclear, careful analysis of the primary genomic fusion sequence has suggested a number of possible mechanisms. These include, aberrant VDJ recombinase activity, topoisomerase II-mediated breakage followed by erroneous end joining, illegitimate recombination mediated by repetitive DNA sequences, proteins that bind to specific DNA binding sites and errors in nonhomologous end joining following double-stranded DNA breaks. Fusions detected to date include the MLL-AF4 fusion in infantile ALL, the TEL-AML1 in childhood ALL and the AML1-ETO and MLL-CALM in childhood AML. While events leading to the formation of chimaeric fusion genes occur in utero, only a few develop clinically overt leukaemia at a later date in early childhood. This suggests that additional postnatal genetic hits are required in preleukaemic cells. Murine models of TEL-AML1 and AML1-ETO support this hypothesis, as the transgenes are insufficient themselves to induce leukaemia.