t(7;9)(q11;p13) PAX5/ELN
2007-04-01 Marina Bousquet , Nicole Dastugue , Pierre Brousset Affiliation1.INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Place Baylac, 31059 Toulouse Cedex, France.
Clinics and Pathology
Disease
B-cell acute lymphoblastic leukemia (B-ALL)
Phenotype stem cell 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)
Genes Involved and Proteins
Gene name
PAX5 (paired box gene 5)
Location
9p13.2
Dna rna description
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 description
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 description
ELN locus spans approximately 40kb and contains 33 exons.
Protein description
ELN is a 72-kDa insoluble extracellular matrix protein.
Result of the Chromosomal Anomaly
Description
5PAX5-3ELN, 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 protocole
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.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37930337 | 2024 | Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL. | 91 |
| 30257940 | 2018 | PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice. | 37 |
| 24507461 | 2014 | PAX5 fusion genes in t(7;9)(q11.2;p13) leukemia: a case report and review of the literature. | 15 |
| 17179230 | 2007 | A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17179230 | 2007 | A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5. | Bousquet M et al |
Summary
Fusion gene
PAX5/ELN PAX5 (9p13.2) ELN (7q11.23) M t(7;9)(q11;p13)|PAX5/ELN PAX5 (9p13.2) ELN (7q11.23) TIC
t(7;9)(q11;p13) RHG-banding (Courtesy Nicole Dastugue).
Citation
Marina Bousquet ; Nicole Dastugue ; Pierre Brousset
t(7;9)(q11;p13) PAX5/ELN
Atlas Genet Cytogenet Oncol Haematol. 2007-04-01
Online version: http://atlasgeneticsoncology.org/haematological/1195/t(7
