t(9;22)(p13;q13) PAX5/BRD1

2014-03-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


B-cell acute lymphoblastic leukemia (ALL)


Only one case to date, a 2-years old boy wit h a CD10+ ALL (Nebral et al., 2009).


The patient was considered as at intermediate risk. He remains in complete remission 44 months after diagnosis.

Genes Involved and Proteins

Gene name
PAX5 (paired box gene 5)
Protein description
391 amino acids; from N-term to C-term, PAX5 contains: a paired domain (aa: 16-142); an octapeptide (aa: 179-186); a partial homeodomain (aa: 228-254); a transactivation domain (aa: 304-359); and an inhibitory domain (aa: 359-391). Lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and repress genes involved in other lineage commitments. Activates the surface cell receptor CD19 and repress FLT3. Pax5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007; Medvedovic et al., 2011). , BRD1 is a subunit of the MOZ histone acetyl transferase (HAT) complex. The MOZ HAT functions is a multi-protein complex with BRD1, ING5 (inhibitor of growth 5, 2q37.3), and MEAF6 (MYST/Esa1-Associated Factor 6, 1p34.3). BRD1 links the MOZ catalytic subunit to the ING5 and MEAF6 subunits, and promotes MOZ HAT activity. The bromodomain of BRD1 acetylates lysine residues of histones H3, H4, H2A, and H2B (H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H2AK5ac). The PWWP domain of BRD1 is the binding module for trimethylation of Lys36 of histone H3 (H3K36me3) associated with the elongation phase of transcription (Vezzoli et al., 2010). There are different splice variants, which are induced differentially in different brain regions (Fryland et al., 2012). The variant BRPF2 may be a negative regulatory factor of the variant BRPF1. BRD1 is widely expressed in various tissues, the brain in particular (in the cell nucleus, perikaryal cytosol and proximal dendrites of the neurons), with high expression at early embryonic stages (Severinsen et al., 2006; Bjarkam et al., 2009). BRD1 has a central role during embryonic development through Moz-dependent histone acetylation, to maintain expression of Hox genes (Laue et al., 2008). BRD1 forms a novel HAT complex with KAT7 (HBO1, 17q21.33) and is required for transcriptional activation of erythroid developmental regulator genes (Mishima et al., 2011). BRD1 showed association with schizophrenia and bipolar affective disorder susceptibility (Bjarkam et al., 2009).
Gene name
BRD1 (bromodomain containing 1)
Protein description
1058 amino acids (aa); from N-term to C-term, BRD1 contains a zinc finger PHD-type (aa 214-264); a bromo domain (aa 579-649) (recognizes acetylated lysine residues; prerequisite for protein-histone association and chromatin remodeling); a PWWP domain (aa 929-1012) (conserved Pro-Trp-Trp-Pro motif; binds histones independently of their acetylation, also binds DNA). Phosphoserines are at aa 128, 1052, and 1055, and N6-acetyllysine at aa 368, 516, 519, and 903. BN1 and BN2 (BRPF N-terminal conserved region 1 and 2) (aa 60-222) is the domain binding MOZ/MORF (Ullah et al., 2008). An enhancer of polycomb homology region (EPL1) (EPL1 protein are members of histone acetyltransferase complex) , which binds to ING5 and mediates association with MEAF6, is located from amino acids 540 and 640 (Ullah et al., 2008).

Result of the Chromosomal Anomaly


Fusion of PAX5 exon 5 to BRD1 non coding exon 1.
Atlas Image
PAX5/BRD1 fusion protein.


1264 amino acids, according to the authors. The predicted fusion protein contains the DNA binding paired domain and octapeptide of PAX5 (201 aa), 4 amino acids, and the entire BRD1 (1058 aa).


Pubmed IDLast YearTitleAuthors
197636152009Further immunohistochemical characterization of BRD1 a new susceptibility gene for schizophrenia and bipolar affective disorder.Bjarkam CR et al
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
226757302012Electroconvulsive seizures regulates the Brd1 gene in the frontal cortex and hippocampus of the adult rat.Fryland T et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
184692222008The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity.Laue K et al
219709552011Pax5: a master regulator of B cell development and leukemogenesis.Medvedovic J et al
217531892011The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis.Mishima Y et al
190205462009Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia.Nebral K et al
169242672006Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder.Severinsen JE et al
187943582008Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes.Ullah M et al
204009502010Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1.Vezzoli A et al
166801442006Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.Zhang Z et al


Fusion gene

PAX5/BRD1 PAX5 (9p13.2) BRD1 (22q13.33) M t(9;22)(p13;q13)|PAX5/BRD1 PAX5 (9p13.2) BRD1 (22q13.33) TIC


Jean-Loup Huret

t(9;22)(p13;q13) PAX5/BRD1

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1562/t(9;22)(p13;q13)

External Links