| Written | 2007-04 | Marina Bousquet, Nicole Dastugue, Pierre Brousset |
| INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Place Baylac, 31059 Toulouse Cedex, France. |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9811/3 B lymphoblastic leukaemia/lymphoma, NOS |
| Atlas_Id | 1195 |
 | |
| t(7;9)(q11;p13) RHG-banding (Courtesy Nicole Dastugue). | |
| Clinics and Pathology |
| Disease | B-cell acute lymphoblastic leukemia (B-ALL) |
| Phenotype / cell stem origin | Pre-B3 phenotype (CD10+ Cmu+) and pre-B2 phenotype (CD10+ Cmu-) |
| Embryonic origin | Only two cases described: a 38-year-old male patient and a 16-year-old male patient. |
| Treatment | GRAAL 2003 trial and LALA94 trial |
| Evolution | Relapse post allograft for both patients |
| Prognosis | Poor (16 months survival for both patients) |
| Cytogenetics |
| Additional anomalies | del(9)(p11p13) in 1 of 2 cases but without PAX5 deletion |
| Genes involved and Proteins |
| Gene Name | PAX5 (paired box gene 5) |
| Location | 9p13.2 |
| Dna / Rna | The PAX5 locus spans approximately 200kb. PAX5 contains 10 exons and two distinct promoters resulting in two alternative 5' exons (1a and 1b). PAX5b is transcribed in the central nervous system and testis as well as in the B lymphoid lineage. PAX5a, also named B-cell specific activator protein (BSAP), is specifically transcribed in the B lymphoid lineage. |
| Protein | PAX5 is a member of the highly conserved paired box (PAX)-domain family of transcription factors. The PAX5 plays an important role in cell differentiation and in embryonic development. PAX5 is expressed from early stages of B-cell development up to mature B-cells and is down-regulated during terminal differentiation into plasma cells. PAX5 contains a paired box domain (DNA binding domain), a conserved octapeptide motif and a partial homeodomain. Its C-terminal region contains a transcriptional activation domain and the extreme C-terminal region acts as a repression domain. |
| Gene Name | ELN (elastin) |
| Location | 7q11.23 |
| Dna / Rna | ELN locus spans approximately 40kb and contains 33 exons. |
| Protein | ELN is a 72-kDa insoluble extracellular matrix protein. |
| Result of the chromosomal anomaly |
| Description | 5'PAX5-3'ELN, PAX5 exon 7 is fused in frame with ELN exon 2. |
| Transcript | The same PAX5-ELN transcript was amplified for both patients. Of note, the two alternative transcripts PAX5a-ELN and PAX5b-ELN were presents. The reciprocal ELN-PAX5 fusion transcript could not be amplified. |
| Detection | The fusion transcript can be detected by RT-PCR using the 5' PAX5 sense primer: 5'-CCCTGTCCATTCCATCAAGTCCTG-3'; the 3' ELN antisense primer 5'-ATGAGGTCGTGAGTCAGGGGTC-3'. |
 | |
| Schematic representation of PAX5-ELN chimera. (A) Sequence of the in-frame fusion between exon 7 of PAX5 and exon 2 of ELN. (B) Structure of PAX5, PAX5-ELN and ELN proteins. PBD, Paired box domain; OCT, octapeptide; NLS, nuclear localization sequence; TD, transactivation domain; RD, repressor domain. | |
| Description | The PAX5-ELN fusion protein conserves the DNA binding domain of PAX5 and its NLS, but looses its transactivation and repression domain. The quasi entire sequence of ELN is preserved without its signal peptide. |
| Expression Localisation | In HeLa cells transfected with the construction PAX5-ELN, the chimera is localized in the nucleus. |
| Oncogenesis | PAX5-ELN acts as a dominant negative on wild-type PAX5 in in vitro experiments that could explain the blockade of differentiation in leukemic cells. |
| 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 |
| A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5. |
| Bousquet M, Broccardo C, Quelen C, Meggetto F, Kuhlein E, Delsol G, Dastugue N, Brousset P |
| Blood. 2007 ; 109 (8) : 3417-3423. |
| PMID 17179230 |
| Citation |
| This paper should be referenced as such : |
| Bousquet, Marina ; Dastugue, Nicole ; Brousset, Pierre |
| t(7;9)(q11;p13) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):316-318. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0709q11p13ID1195.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | KMT2A |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(7;9)(q11;p13) PAX5/ELN | |
| External links |
| Mitelman database | t(7;9)(q11;p13) [Case List] t(7;9)(q11;p13) [Transloc-MCList] PAX5/ELN [Fusion-MCList] |
| arrayMap (UZH-SIB Zurich) | Topo ( C42) Morph ( 9811/3) - [auto + random 100 samples .. if exist ] [tabulated segments] |
| Mitelman database | PAX5/ELN [MCList] PAX5 (9p13.2) ELN (7q11.23) |
| TICdb | PAX5/ELN PAX5 (9p13.2) ELN (7q11.23) |
| 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 May 14 13:40:05 CEST 2018 |
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