| Written | 2013-03 | Andrew L Feldman |
| Department of Laboratory Medicine, Pathology, College Of Medicine, Mayo Clinic, 200 First Street SW, Hilton Building, Room 11-52D, Rochester, MN 55905 USA |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| Atlas_Id | 1606 |
| Clinics and Pathology |
| Disease | Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) |
| Phenotype / cell stem origin | Mature (peripheral) cytotoxic alpha-beta T-cell origin. |
| Etiology | No etiologic factors are known. |
| Epidemiology | Adult males (age range, 67-82 years). |
| Clinics | Presentation with cytopenias in the absence of lymphadenopathy, sometimes with skin involvement. |
| Pathology | The bone marrow is hypercellular with the normal marrow elements replaced by an extensive infiltrate of atypical, mostly medium-sized lymphoid cells with irregular nuclear outlines. Admixed plasma cells and a background of reticulin fibrosis are present. The tumor cells display an abnormal T-cell phenotype with expression of CD3, the cytotoxic marker TIA1 (+/- granzyme B), and T-cell receptor-beta (beta-F1), but without coexpression of CD5. Most cases express CD4 and lack expression of CD25 and CD30. IRF4/MUM1 protein is expressed in tumor cell nuclei. Cases tested for EBV by in situ hybridization have been negative. |
 | |
| (A) Atypical lymphocytes in bone marrow smear from patient with PTCL, NOS with t(6;14)(p25.3;q11.2) (Wright-Giemsa, original magnification x1000). (B) Bone marrow trephine biopsy (H&E, x400). Tumor cells are (C) positive for CD2, (D) negative for CD5, (E) positive for granzyme B, and (F) positive for nuclear IRF4/MUM1 (x400). | |
| Treatment | No treatment data are available. |
| Prognosis | The prognosis has not been established. |
| Cytogenetics |
| Cytogenetics Morphological | The rearrangement can be detected in standard G-banded karyotype. |
 | |
| t(6;14)(p25.3;q11.2) [G-banding]. | |
| Cytogenetics Molecular | The rearrangement can be detected using dual-fusion fluorescence in situ hybridization with probes to the IRF4 and TCR@ loci. |
| Genes involved and Proteins |
| Note | The IRF4/MUM1 protein is expressed in cases with t(6;14)(p25.3;q11.2). This expression likely results from the translocation, but this has not been proved. |
| Gene Name | IRF4 (interferon regulatory factor 4) |
| Location | 6p25.3 |
| Dna / Rna | Nine-exon gene on 6p25.3. |
| Protein | The gene encodes interferon regulatory factor-4 (IRF4)/multiple myeloma oncogene-1 (MUM1), a transcription factor in the IRF family. Its expression limited mainly to lymphocytes and is critical in lymphocyte activation. |
| Gene Name | TRA (T cell Receptor Alpha) |
| Location | 14q11.2 |
| Note | Other name: TRA@. |
| Dna / Rna | ~ 1Mb on 14q11.2 containing TCR alpha V, J, and C regions, as well as the TCR-delta locus. |
| Protein | TRA@ encodes the T-cell receptor-alpha chains, translated from transcripts resulting from rearrangement of the TRAV and TRAJ regions and from TRAC. |
| Result of the chromosomal anomaly |
| Note | No RNA studies have been reported on cases with t(6;14)(p25.3;q11.2). Most translocations involving TRA@ in T-cell neoplasia do not produce fusion transcripts. |
| Note | No studies of potential fusion proteins have been reported on cases with t(6;14)(p25.3;q11.2). Most translocations involving TRA@ in T-cell neoplasia do not produce fusion proteins. |
| To be noted |
| Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section. |
| Bibliography |
| Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. |
| Feldman AL, Law M, Remstein ED, Macon WR, Erickson LA, Grogg KL, Kurtin PJ, Dogan A. |
| Leukemia. 2009 Mar;23(3):574-80. doi: 10.1038/leu.2008.320. Epub 2008 Nov 6. |
| PMID 18987657 |
| IRF4: Immunity. Malignancy! Therapy? |
| Shaffer AL, Emre NC, Romesser PB, Staudt LM. |
| Clin Cancer Res. 2009 May 1;15(9):2954-61. doi: 10.1158/1078-0432.CCR-08-1845. Epub 2009 Apr 21. (REVIEW) |
| PMID 19383829 |
| Citation |
| This paper should be referenced as such : |
| Feldman, AL |
| t(6;14)(p25.3;q11.2) TRA/IRF4 |
| Atlas Genet Cytogenet Oncol Haematol. 2013;17(9):645-646. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0614p25q11ID1606.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(6;14)(p25.3;q11.2) TRA/IRF4 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Aug 12 17:00:19 CEST 2019 |
For comments and suggestions or contributions, please contact us