Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations

Abstract

T-cell prolymphocytic leukemia (T-PLL), a rare form of mature T-cell leukemias, and ataxia telangiectasia clonal proliferation, a related condition occurring in patients suffering from ataxia telangiectasia, have been associated to translocations involving the 14q32.1 or Xq28 regions, where are located the TCL1 and MTCP1 putative oncogenes, respectively. The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation associated with these T-cell proliferations. Alternative splicing generates type A and B transcripts that potentially encode two entirely distinct proteins; type A transcripts code for a small mitochondrial protein, p8MTCP1, and type B transcripts, containing an additional open reading frame, may code for 107 amino-acid protein, p13MTCP1. The recently cloned TCL1 gene, also involved in translocations and inversions associated with T-cell proliferations, codes for a 14-kD protein that displays significant homology with p13MTCP1. We have generated rabbit antisera against this putative p13MTCP1 protein and screened for expression of p13MTCP1 normal lymphoid tissues and 33 cases of immature and mature lymphoid T-cell proliferations using a sensitive Western blot assay. We also investigated the MTCP1 locus configuration by Southern blot analysis. The p13MTCP1 protein was detected in the three T-cell proliferations with MTCP1 rearrangements because of t(X;14) translocations, but neither in normal resting and activated lymphocytes nor in the other T- cell leukemias. Our data support the hypothesis that p13MTCP1 and p14TCL1 form a new protein family that plays a key role in the pathogenesis of T-PLL and related conditions.

Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T‐cell prolymphocytic leukemia

“…The t(X;14)(q28;q11) is associated with deregulation MTCP-1 B1 gene (by jux-taposition to a T-cell receptor gene). Abnormalities involving the band Xq28 (the site for the MCTP-1B1 gene, which has homology to TCL-1 on 14q32.1) are common in T-PLL (Madani et al, 1996). Rearrangements associated to TCR genes also result in juxtaposition of enhancer elements, responsible for TCR genes expression, next to different oncogene loci, leading to disruption of transcriptional pathways involved in normal T-cell development, and ultimately, leukemic transformation (Brito-Babapulle & Catovsky, 1991).…”

Genes encoding members of the JAK‐STAT pathway or epigenetic regulators are recurrently mutated in T‐cell prolymphocytic leukaemia

“…The primary genetic alteration in T-PLL is the inv(14)(q11q32), its variant t(14;14)(q11;q32) or, less commonly, the translocation t(X;14)(q28;q11). These chromosomal aberrations juxtapose the TRA/TRD locus in 14q11 to the oncogenes TCL1A (14q32) and MTCP1 (Xq28) (Fisch et al, 1993;Stern et al, 1993;Madani et al, 1996;de Oliveira et al, 2009). Although these translocations consistently characterize the majority of T-PLL and seem to occur early in the pathogenesis, alone they are probably insufficient to drive T-PLL leukaemogenesis.…”

Indolent course as a relatively frequent presentation in T‐prolymphocytic leukaemia

“…These abnormalities juxtapose the TCL-1 (located at 14q32) or MTCP-1 (located at Xq28) genes to the TCR a/d locus on 14q11 (Stern et al, 1993;Virgilio et al, 1994), resulting in overexpression of p14 TCL1 and p13 MTCP1 which share structural homology (Stern et al, 1993;Fu et al, 1994). p13 MTCP1 , but not p14 TCL1 , is restricted to T-PLL cells (Madani et al, 1996). Interestingly, an aggressive T-cell disorder with similar clinical and laboratory features, as well as identical cytogenetic abnormalities, has been described in a rare genetic condition, ataxia-telangectasia (AT) (Britto-Babapulle et al, 1991;Taylor et al, 1996).…”