Exon/intron structure of the human AF‐4 gene, a member of the AF‐4/LAF‐4/FMR‐2 gene family coding for a nuclear protein with structural alterations in acute leukaemia

The AF‐4 gene on human chromosome 4q21 is involved in reciprocal translocations to the ALL‐1 gene on chromosome 11q23, which are associated with acute lymphoblastic leukaemias. A set of recombinant phage carrying genomic fragments for the coding region and flanking sequences of the AF‐4 gene were isolated. Phage inserts were assembled into four contigs with 21 exons, and an intron phase map was produced enabling the interpretation of translocation‐generated fusion proteins. The gene contains two alternative first exons, 1a and 1b, both including a translation initiation codon. The translocation breakpoint cluster region is flanked by exons 3 and 6 and two different polyadenylation signals were identified. Polyclonal antisera directed against three different portions of the AF‐4 protein were produced and used to detect a 116 kD protein in cellular extracts of human B‐lymphoblastoid and proB cell lines. In mitogen‐stimulated human peripheral blood mononuclear cells the AF‐4 antigen was predominantly located in the nucleus. The AF‐4 gene is a member of the AF‐4, LAF‐4 and FMR‐2 gene family. The members of this family encode serine‐proline‐rich proteins with properties of nuclear transcription factors. Comparison of AF‐4 protein coding sequences with the LAF‐4 and FMR‐2 sequences revealed five highly conserved domains of potential functional relevance.