Genomic organization, tissue expression, and cellular localization of AF3p21, a fusion partner of MLL in therapy-related leukemia.

We previously identified the AF3p21 gene, a novel fusion partner of the MLL gene, in a patient who had developed therapy-related leukemia with t(3;11)(p21;q23). The AF3p21 gene encodes a protein consisting of 722 amino acids, which has an SH3 (Src homology 3) domain, a proline-rich domain, and a bipartite nuclear localization signal. The protein's SH3 domain has high homology with that of FYN. Analysis of the DNA from the patient's leukemic cells revealed that intron 6 of the MLL gene was fused at a point upstream of exon 1 in the AF3p21 gene, and that the der(11) chromosome formed an MLL-AF3p21 fusion transcript in leukemic cells, whereas the der(3) chromosome did not form any fusion transcript. The AF3p21 gene on chromosome band 3p21 is 19 kb long and consists of 13 exons. The size of the mRNA of the AF3p21 gene is approximately 3.5 kb. The AF3p21 gene is widely expressed in normal human tissues including the bone marrow, brain, liver, thymus, lung, and skeletal muscle. Western blot and immunocytochemical analyses showed that AF3p21 protein has an apparent molecular weight of 80 kDa and is localized exclusively in the cell nucleus. These results suggest the possibility that AF3p21 protein plays a role in signal transduction in the nucleus.