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The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation associated with T-cell prolymphocytic leukemia and related conditions. This gene is unusual in that it codes for two distinct proteins: a small mitochondrial protein, p8MTCP1, and a putative oncogenic protein, p13MTCP1. Scarcity of material from t(X;14)-associated proliferations and very low levels of mRNA expression have so far prevented a thorough description of p13MTCP1-encoding transcripts. Here, we characterize two additional t(X;14) bearing leukemias allowing this analysis. In one case, with a breakpoint located 5′ to the MTCP1 gene, the level of transcription of previously described p13MTCP1-encoding transcripts is enhanced. 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 duplication of an ancestral gene was followed by the insertion of one copy within the intron of a p8-encoding gene, accounting for the unusual feature of the MTCP1 gene. [ABSTRACT FROM AUTHOR]

Objective: Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance. Methods: The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR). Results: Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery. Conclusion: The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term. [Copyright &y& Elsevier]