Atlas of Genetics and Cytogenetics in Oncology and Haematology
t(7;9)(q11;p13)
| Identity |
 | |
| 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-) |
| Treatment | GRAAL 2003 trial and LALA94 trial |
| Evolution | Relapse post allograft for both patients |
| Prognosis | Poor (16 months survival for both patients) |
| Cytogenetics |
| Probes | BAC probes: RP11-243F8 for PAX5 and CTD-2278A11 for ELN |
| Additional anomalies | del(9)(p11p13) in 1 of 2 cases but without PAX5 deletion |
| Genes involved and Proteins |
| Gene Name | PAX5 |
| Location | 9p13 |
| 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 |
| Location | 7q11 |
| 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 | 5¹PAX5-3¹ELN, 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-3¹and the 3' ELN antisense primer 5¹-ATGAGGTCGTGAGTCAGGGGTC-3¹. |
 | |
| 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. |
| 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. |
| External links |
| Other database | t(7;9)(q11;p13) | Mitelman database (CGAP - NCBI) | |
| Other database | t(7;9)(q11;p13) | CancerChromosomes (NCBI) |
| 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 |
| Contributor(s) |
| Written | 04-2007 | Marina Bousquet, Nicole Dastugue, Pierre Brousset |
| INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Place Baylac, 31059 Toulouse Cedex, France. |
| Citation |
| This paper should be referenced as such : |
| Bousquet M, Dastugue N, Brousset P . t(7;9)(q11;p13). Atlas Genet Cytogenet Oncol Haematol. April 2007 . URL : http://AtlasGeneticsOncology.org/Anomalies/t0709q11p13ID1195.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon May 12 18:12:31 2008 |
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