ALTERNATIVE SPLICING IN WILD-TYPE AF10 AND CALM CDNAS AND IN AF10-CALM AND CALM-AF10 FUSION CDNAS PRODUCED BY THE T(10-11)(P13-14-Q14-Q21) SUGGESTS A POTENTIAL ROLE FOR TRUNCATED AF10 POLYPEPTIDES

The t(10;11)(p13;q14-21) is a non-random translocation that occurs pri marily in T cell acute lymphoblastic leukemias (TALL), but has also be en observed in leukemias and lymphomas of diverse lineages. In U937, a cell line established from a diffuse histiocytic lymphoma, a t(10;11) (p13;q14-21) fuses AF10 to CALM. AF10 is also fused to MLL by a transl ocation that appears quite similar at the cytogenetic level, the t(10; 11)(p12;q23). Fluorescence in situ hybridization studies have demonstr ated that AF10 and CALM are also involved in other hematological malig nancies containing t(10;11)(p13;q21), but no data are available concer ning the molecular details of AF10-CALM fusion in primary leukemias. U sing RT-PCR, we amplified multiple different isoforms of AF10-CALM and CALM-AF10 fusion cDNAs from a primary T cell ALL containing a t(10;11 )(p13-14;q14-21). These cDNAs arose via alternative splicing of exons from both AF10 and CALM, which we demonstrated can also occur in the n ative genes. We identified at least two novel AFIO exons that can be i ncluded in wild-type and fusion cDNAs. The majority of the AF10 and AF 10-CALM cDNA isoforms that we identified are predicted to encode for t runcated AF10 polypeptides, raising the possibility that these might h ave important cellular functions in normal and malignant cells, perhap s by acting as dominant negative inhibitors of full-length AF10 or rel ated proteins.