t(9;9)(p13;p24) PAX5/JAK2
del(9)(p13p24) PAX5/JAK2
inv(9)(p13p24) PAX5/JAK2

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 (B-ALL)

Phenotype stem cell origin

Three cases were CD10+, and one case was Cμ.

Embryonic origin

Only four cases to date (Nebral et al., 2009; Coyaud et al., 2010; Roberts et al., 2012).


This chromosome abnormality has only been found so far in childhood B-ALL: there were 2 male and 2 female patients, aged 7, 10, 13 and 14 years.


Two of three patients were considered as being at high risk, and one at intermediate risk. One patient was in complete remission (CR) 65 months after diagnosis, and another one was in a second CR at 10 months+ (Nebral et al., 2009).

Genes Involved and Proteins

Gene name
JAK2 (janus kinase 2)
Protein description
1132 amino acids (aa); from N-term to C-term, JAK2 contains: an interaction region with cytokine/interferon/growth hormone receptors: aa 1-239, a FERM domain: aa 37-380, a SH2 domain: aa 401-482, two protein kinase domains: aa 545-809 and 849-1124, an ATP nucleotide binding site: aa 855-863, and a loop structure: aa 1056-1078 (JAK2 kinase insertion loop). JAK homology domains are the following: JH7: aa 25-137; JH6: aa 144-284; JH5: aa 288-309; JH4: aa 322-440; JH3: aa 451-538; JH2: aa 543-824; JH1: 836-1123. Phosphotyrosines are located at aa 119, 372, 373, 523, 813, 868, 966, 972, 1007, and 1008 (Harpur et al., 1992; Saltzman et al., 1998; Lucet et al., 2006). Protein tyrosine kinase of the non-receptor type that associates with the intracellular domains of cytokine receptors; Mediates signaling transduction.
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).

Result of the Chromosomal Anomaly


Fusion of PAX5 exon 5 to JAK2 exon 19 in each case. Opposite direction is noted by Coyaud et al., 2010.
Atlas Image
PAX5/JAK2 fusion protein.


522 amino acids (201 from PAX5 and 321 from JAK2). The predicted fusion protein contains the DNA binding paired domain of PAX5 and the Protein kinase 2 domain from JAK2 (breakpoint at aa 811 or 812 in JAK2).


Pubmed IDLast YearTitleAuthors
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
201601642010Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.Coyaud E et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
16205481992JAK2, a third member of the JAK family of protein tyrosine kinases.Harpur AG et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
161747682006The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.Lucet IS et al
219709552011Pax5: a master regulator of B cell development and leukemogenesis.Medvedovic J et al
190205462009Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia.Nebral K et al
228978472012Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.Roberts KG et al
96182631998Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue.Saltzman 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/JAK2 PAX5 (9p13.2) JAK2 (9p24.1) COF 1071 1072|PAX5/JAK2 PAX5 (9p13.2) JAK2 (9p24.1) M del(9)(p13) del(9)(p13p24) del(9)(p24) inv(9)(p13p24) t(9;9)(p13;p24)|PAX5/JAK2 PAX5 (9p13.2) JAK2 (9p24.1) TIC


Jean-Loup Huret

t(9;9)(p13;p24) PAX5/JAK2
del(9)(p13p24) PAX5/JAK2
inv(9)(p13p24) PAX5/JAK2

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1559/del(9)(p13p24)

External Links