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PAX5/ETV6 alters the gene expression profile of precursor B cells with opposite dominant effect on endogenous PAX5

Leukemia volume 27, pages 992–995 (2013)Cite this article

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The PAX5 gene encodes for a transcription factor essential for B-cell development,1, 2 which has been recently reported as frequent target of aberrancies, including mutations, deletions and translocations in ∼30% of pediatric patients with B-cell precursor acute lymphoblastic leukemia.3, 4 Among several translocations with different partner genes, the t(9;12) encoding for the PAX5/ETV6 fusion, is the most recurrent.2

The role of PAX5/ETV6 in leukemogenesis is not fully understood, although preliminary evidences suggested that the protein may have a repressor function on transcription.3, 5, 6 The PAX5/ETV6 protein retains the ability to interact with the PAX5-consensus sequence contained in the CD19 promoter,6 and it is able to multimerize and bind the PAX5-consensus sequence with high affinity, determining a dominant negative activity on wt PAX5.7

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Acknowledgements

This work was supported by grants from Associazione Italiana Ricerca sul Cancro (AIRC) and Federazione Italiana Ricerca sul Cancro (FIRC), Fondazione Cariplo, MIUR, UNIMIB, Associazione Gianfranco Lupo. We thank Dr Cristina Bugarin (Centro Ricerca Tettamanti, Clinica Pediatrica Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy) for the sorting procedures.

Authors contribution

FG, as post-doc researcher, developed the study, designed the experimental plan, carried out the assays and wrote the manuscript; moreover, she coordinated the work of CV (PhD student), who contribute to the study, especially on bioinformatics analysis and functional assays. PC contributed to the adhesion assay setup and to scientific discussion. Galbiati M performed the image acquisition and analyses of adhesion assays. Giordan M and te KG performed the statistical analysis of microarray data. RA was involved in the in vitro model development and contributed to the scientific discussion of the project. BA and CG share the senior authorship of this paper, they coordinated the study, with scientific supervision and discussions, helped to interpret the results and contributed to the revision of the manuscript.

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Author notes

  1. A Biondi and G Cazzaniga: These authors share the senior authorship of this paper.

Authors and Affiliations

  1. Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy

    G Fazio, V Cazzaniga, C Palmi, M Galbiati, A Biondi & G Cazzaniga

  2. Laboratorio di Oncoematologia, Clinica Pediatrica, Università di Padova, Padova, Italy

    M Giordan & G te Kronnie

  3. Department of Biomedicine, University of Basel, Basel, Switzerland

    A Rolink

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  1. G Fazio
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  2. V Cazzaniga
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  4. M Galbiati
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  7. A Biondi
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  8. G Cazzaniga
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Corresponding author

Correspondence to G Cazzaniga.

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The authors declare no conflict of interest.

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Fazio, G., Cazzaniga, V., Palmi, C. et al. PAX5/ETV6 alters the gene expression profile of precursor B cells with opposite dominant effect on endogenous PAX5. Leukemia 27, 992–995 (2013). https://doi.org/10.1038/leu.2012.281

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