Abstract
Recurrent chromosomal abnormalities present in malignant cells often define subentities with unique biological and clinical features. The molecular identification of genes involved in genetic alterations has led to the characterization of fusion genes with neoplastic properties. However, for many nonrandom translocations including the dic(9;12)(p11–13;p11–12), the molecular equivalent has not as yet been identified. The dicentric translocation dic(9;12) is a recurrent chromosome abnormality that accounts for close to 1% of childhood acute lymphoblastic leukemia (ALL). This specific alteration occurs almost exclusively in B-progenitor ALL, and unlike many other nonrandom translocations, is associated with an excellent prognosis. In this work, we provide strong evidence that the PAX5/ETV6 fusion transcript defines the clinical and biological entity that is associated with the presence of a dic(9;12) chromosome. As the PAX5 and ETV6 genes are localized at 9p13 and 12p13, respectively, the cytogenetic description of the dic(9;12)-PAX5/ETV6 rearrangement should be refined to dic(9;12)(p13;p13).
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Carroll AJ, Raimondi SC, Williams DL, Behm FG, Borowitz M, Castleberry RP et al. tdic(9;12): a nonrandom chromosome abnormality in childhood B-cell precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood 1987; 70: 1962–1965.
Behrendt H, Charrin C, Gibbons B, Harrison CJ, Hawkins JM, Heerema NA et al. Dicentric (9;12) in acute lymphocytic leukemia and other hematological malignancies: report from a dic(9;12) study group. Leukemia 1995; 9: 102–106.
Mahmoud H, Carroll AJ, Behm F, Raimondi SC, Schuster J, Borowitz M et al. The non-random dic(9;12) translocation in acute lymphoblastic leukemia is associated with B-progenitor phenotype and an excellent prognosis. Leukemia 1992; 6: 703–707.
ISCN. Mitelman F (Ed.). An International System for Human Cytogenetic Nomenclature. Basel: Karger, 1995.
Busslinger M, Klix N, Pfeffer P, Graninger PG, Kozmik Z . Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma. Proc Natl Acad Sci USA 1996; 93: 6129–6134.
Baens M, Peeters P, Guo C, Aerssens J, Marynen P . Genomic organization of TEL: the human ETS-variant gene 6. Genome Res 1996; 6: 404–413.
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E et al. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res 2001; 61: 4666–4670.
Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997; 90: 2535–2540.
Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towatari M et al. Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12).). Blood 2001; 97: 1050–1055.
Andreasson P, Johansson B, Carlsson M, Jarlsfelt I, Fioretos T, Mitelman F et al. BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion. Genes Chromosomes Cancer 1997; 20: 299–304.
Nutt SL, Heavey B, Rolink AG, Busslinger M . Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 1999; 401: 556–562.
Mikkola I, Heavey B, Horcher M, Busslinger M . Reversion of B cell commitment upon loss of Pax5 expression. Science 2002; 297: 110–113.
Nutt SL, Morrison AM, Dorfler P, Rolink A, Busslinger M . Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments. EMBO J 1998; 17: 2319–2333.
Acknowledgements
This work was supported by grants of the ‘Österreichische Kinderkrebshilfe’ and private donations.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Strehl, S., König, M., Dworzak, M. et al. PAX5/ETV6 fusion defines cytogenetic entity dic(9;12)(p13;p13). Leukemia 17, 1121–1123 (2003). https://doi.org/10.1038/sj.leu.2402923
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2402923
Keywords
This article is cited by
-
Advances in germline predisposition to acute leukaemias and myeloid neoplasms
Nature Reviews Cancer (2021)
-
A patient with B-cell acute lymphoblastic leukemia with PAX5-ETV6 rearrangement with dic(9;12)(p13;p13) identified by chromosomal microarray
Annals of Hematology (2018)
-
Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes
International Journal of Hematology (2018)
-
PAX5-KIAA1549L: a novel fusion gene in a case of pediatric B-cell precursor acute lymphoblastic leukemia
Molecular Cytogenetics (2015)
-
PAX genes in childhood oncogenesis: developmental biology gone awry?
Oncogene (2015)