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t(9;15)(p13;q24) PAX5::PML

Written2014-01Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1561
Note The translocation is noted with various breakpoints on chromosome 15, ranging from q22 to q25 (this is reminiscent of the t(15;17) PML/RARA).

Clinics and Pathology

Disease B-cell acute lymphoblastic leukemia (B-ALL)
Epidemiology Two cases to date, a 9-month old girl and a 1.5-year old boy, both with a CD10+ ALL (Nebral et al., 2007; Nebral et al., 2009).
Prognosis A patient remains in complete remission 84 months from diagnosis, while the other one had a testicular relapse 2 years after diagnosis and died.


Cytogenetics Morphological The translocation was the sole abnormality.

Genes involved and Proteins

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).
Gene NamePML (promyelocytic leukemia)
Location 15q24.1
Protein 882 amino-acids (aa) and shorter isoforms with distinct C terminus sequences; from N-term to C-term, PML contains: a proline rich domain (aa 3-46); a zinc finger (RING finger type) (aa 57-92); two zinc fingers (B-box types) (aa 124-166 and aa 183-236); a coiled coil made of hydrophobic aa heptad repeats (aa 228-253); an interaction domain with PER2 (aa 448-555); a nuclear localization signal (aa 476-490); a proline rich domain (aa 504-583); a serine rich domain (aa 506-540); and a sumo interaction motif (aa 556-562). The RING finger, B-boxes, and coiled-coil region form a tripartite motif known as the TRIM or the RBCC motif, and is associated with E3 ubiquitin ligase activity. PML is the organizer of nuclear domains called nuclear bodies, which recruit a wide variety of proteins, most often sumoylated. PML is involved in DNA damage response, cell division control, chromosome instability, and is a clock regulator via regulation of PER2 expression. PML has pro-apoptotic functions, induces senescence, inhibits angiogenesis and cell migration (Grignani et al., 1996; Chen et al., 2012; de Thé et al., 2012).

Result of the chromosomal anomaly

Hybrid gene
Description Fusion of PAX5 exon 6 to PML exon 2.
Fusion Protein
  PAX5/PML fusion protein.
Description 1099 amino acids. The predicted fusion protein contains the DNA binding paired domain of PAX5 (260 aa from PAX5) and most of PML (839 aa).

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.


The role of PML ubiquitination in human malignancies.
Chen RH, Lee YR, Yuan WC.
J Biomed Sci. 2012 Aug 30;19:81. doi: 10.1186/1423-0127-19-81. (REVIEW)
PMID 22935031
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
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
Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains.
Grignani F, Testa U, Rogaia D, Ferrucci PF, Samoggia P, Pinto A, Aldinucci D, Gelmetti V, Fagioli M, Alcalay M, Seeler J, Grignani F, Nicoletti I, Peschle C, Pelicci PG.
EMBO J. 1996 Sep 16;15(18):4949-58.
PMID 8890168
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
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
Identification of PML as novel PAX5 fusion partner in childhood acute lymphoblastic leukaemia.
Nebral K, Konig M, Harder L, Siebert R, Haas OA, Strehl S.
Br J Haematol. 2007 Oct;139(2):269-74.
PMID 17897302
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
The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies.
de The H, Le Bras M, Lallemand-Breitenbach V.
J Cell Biol. 2012 Jul 9;198(1):11-21. doi: 10.1083/jcb.201112044. (REVIEW)
PMID 22778276


This paper should be referenced as such :
JL Huret
t(9;15)(p13;q24) PAX5/PML
Atlas Genet Cytogenet Oncol Haematol. 2014;18(9):682-684.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes PML

Translocations implicated (Data extracted from papers in the Atlas)

 t(9;15)(p13;q24) PAX5/PML

External links

PAX5 (9p13.2) PML (15q24.1)

PAX5 (9p13.2) PML (15q24.1)

Mitelman databaset(9;15)(p13;q24)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databasePAX5::PML [MCList]  PAX5 (9p13.2) PML (15q24.1)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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