ALTERNATIVE ORIGIN OF P13(MTCP1)-ENCODING TRANSCRIPTS IN MATURE T-CELL PROLIFERATIONS WITH T(X-14) TRANSLOCATIONS

The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation assoc iated with T-cell prolymphocytic leukemia and related conditions. This gene is unusual in that it codes for two distinct proteins: a small m itochondrial protein, p8(MTCP1), putative oncogenic protein, p13(MTCP1 ). Scarcity of material from t(X;14)-associated proliferations and ver y low levels of mRNA expression have so far prevented a thorough descr iption of p13(MTCP1)-encoding transcripts. Here, we characterize two a dditional t(X;14) bearing leukemias allowing this analysis. In one cas e, with a breakpoint located 5' to the MTCP1 gene, the level of transc ription of previously described p13(MTCP1)-encoding transcripts is enh anced. In the second case, with a breakpoint within the MTCP1 intron I , an alternative transcription initiation site is demonstrated in the tumor cells at 229 bp upstream to exon II. The identification of this internal promoter, together with the similarity between TCL1 and MTCP1 genomic structures, allow us to propose a model in which the duplicat ion of an ancestral gene was followed by the insertion of one copy wit hin the intron of a p8-encoding gene, accounting for the unusual featu re of the MTCP1 gene.