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t(9;9)(p13;p24) PAX5::JAK2

del(9)(p13p24) PAX5::JAK2

inv(9)(p13p24) PAX5::JAK2

Written2014-03Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1559

Clinics and Pathology

Disease B-cell acute lymphoblastic leukemia (B-ALL)
Phenotype / cell stem 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).
Epidemiology 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.
Prognosis 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).


Cytogenetics Morphological Additional chromosome abnormalities were noted in the two cases with complete data on the karyotypes.

Genes involved and Proteins

Gene NameJAK2 (janus kinase 2)
Location 9p24.1
Protein 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 NamePAX5 (paired box gene 5)
Location 9p13.2
Protein 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

Hybrid gene
Description Fusion of PAX5 exon 5 to JAK2 exon 19 in each case. Opposite direction is noted by Coyaud et al., 2010.
Fusion Protein
  PAX5/JAK2 fusion protein.
Description 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).

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.


Pax5: the guardian of B cell identity and function.
Cobaleda C, Schebesta A, Delogu A, Busslinger M.
Nat Immunol. 2007 May;8(5):463-70. (REVIEW)
PMID 17440452
Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C.
Blood. 2010 Apr 15;115(15):3089-97. doi: 10.1182/blood-2009-07-234229. Epub 2010 Feb 16.
PMID 20160164
Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.
Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M.
Genes Dev. 2004 Feb 15;18(4):411-22.
PMID 15004008
JAK2, a third member of the JAK family of protein tyrosine kinases.
Harpur AG, Andres AC, Ziemiecki A, Aston RR, Wilks AF.
Oncogene. 1992 Jul;7(7):1347-53.
PMID 1620548
B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.
Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K.
Nat Immunol. 2004 Aug;5(8):853-61. Epub 2004 Jul 18.
PMID 15258579
The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.
Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF, Rossjohn J.
Blood. 2006 Jan 1;107(1):176-83. Epub 2005 Sep 20.
PMID 16174768
Pax5: a master regulator of B cell development and leukemogenesis.
Medvedovic J, Ebert A, Tagoh H, Busslinger M.
Adv Immunol. 2011;111:179-206. doi: 10.1016/B978-0-12-385991-4.00005-2. (REVIEW)
PMID 21970955
Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia.
Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas OA, Strehl S.
Leukemia. 2009 Jan;23(1):134-43. doi: 10.1038/leu.2008.306. Epub 2008 Nov 20.
PMID 19020546
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG.
Cancer Cell. 2012 Aug 14;22(2):153-66. doi: 10.1016/j.ccr.2012.06.005.
PMID 22897847
Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue.
Saltzman A, Stone M, Franks C, Searfoss G, Munro R, Jaye M, Ivashchenko Y.
Biochem Biophys Res Commun. 1998 May 29;246(3):627-33.
PMID 9618263
Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.
Zhang Z, Espinoza CR, Yu Z, Stephan R, He T, Williams GS, Burrows PD, Hagman J, Feeney AJ, Cooper MD.
Nat Immunol. 2006 Jun;7(6):616-24. Epub 2006 May 7.
PMID 16680144


This paper should be referenced as such :
JL Huret
t(9;9)(p13;p24) PAX5/JAK2 - del(9)(p13p24) PAX5/JAK2 - inv(9)(p13p24) PAX5/JAK2
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):760-762.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

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

External links

PAX5 (9p13.2) JAK2 (9p24.1)

PAX5 (9p13.2) JAK2 (9p24.1)

PAX5 (9p13.2) JAK2 (9p24.1)

Mitelman databaset(9;9)(p13;p24)
Mitelman databasedel(9)(p13p24)
Mitelman databaseinv(9)(p13p24)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionPAX5/JAK2 PAX5 (9p13.2) JAK2 (9p24.1)   [fusion1071]   [fusion1072]  
Mitelman databasePAX5::JAK2 [MCList]  PAX5 (9p13.2) JAK2 (9p24.1)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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