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KMT2A-ARHGEF12, a therapy related fusion with poor prognosis

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Abstract

Background

The detection of KMT2A gene rearrangements have an important impact on the prognosis and management of acute leukemias. These alterations most commonly involve reciprocal translocations at specific breakpoint regions within KMT2A. To date, more than 100 translocation partner genes of KMT2A have been identified, with different effects on risk stratification.

Methods and results

We report the case of a mature plasmacytoid dendritic cells proliferation associated with B lymphoblasts harboring a KMT2A-ARHGEF12 fusion. This rare rearrangement, resulting from a cryptic deletion on the long arm of chromosome 11, is located outside the known major and minor breakpoint regions of KMT2A, not reported to date. The review of the few cases of KMT2A-ARHGEF12 reveals the tendency of this deletion to occur in therapy related hematologic neoplasm and confer unfavorable prognosis.

Conclusion

This review sheds light into the rare KMT2A-ARHGEF12 fusion in leukemia. Reporting rare chimeras is essential to improve knowledge about the biological mechanism and associated clinical consequences

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Fig. 1

Data Availability

Data presented in this study can be found in the Laboratory Information System of the centre hospitalier de Versailles and the Institute of Pharmaceutical Biology/DCAL, Goethe-University Frankfurt.

Code availability

Not applicable.

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Acknowledgements

The authors would like to thank the Centre Hospitalier de Versailles for editorial assistance.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Hemato-Oncologic Cytogenetics, Centre Hospitalier de Versailles, 2, rue JL Forain, 78150, Le Chesnay, France

    Nada Assaf & Christine Terré

  2. Department of Hematology, Centre Hospitalier de Versailles, Le Chesnay, France

    Raphael Liévin, Fatiha Merabet & Philippe Rousselot

  3. University Paris-Saclay, UMR1184, Gif-sur-Yvette, France

    Raphael Liévin, Fatiha Merabet & Philippe Rousselot

  4. Department of Laboratory Medicine, Hematology, Centre Hospitalier de Versailles, Le Chesnay, France

    Victoria Raggueneau & Jenifer Osman

  5. Hematology Laboratory, Hôpital Saint-Louis, APHP, Paris, France

    Rathana Kim

  6. Université de Paris, INSERM U944, CNRS UMR 7212, Paris, France

    Rathana Kim

  7. Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Besançon, France

    Francine Garnache

  8. Department of Pediatrics, Centro Ricerca Tettamanti, San Gerardo Hospital/Fondazione MBBM, University of Milan Bicocca, Monza, Italy

    Mariella D’Angiò

  9. Institute of Pharmaceutical Biology/DCAL, Goethe-University Frankfurt, Frankfurt am Main, Germany

    Patrizia Larghero, Claus Meyer & Rolf Marschalek

Authors
  1. Nada Assaf
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  2. Raphael Liévin
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  3. Fatiha Merabet
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  4. Victoria Raggueneau
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  5. Jenifer Osman
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  7. Francine Garnache
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  8. Mariella D’Angiò
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  9. Patrizia Larghero
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  10. Claus Meyer
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  11. Rolf Marschalek
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  12. Philippe Rousselot
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  13. Christine Terré
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Contributions

N.A wrote the manuscript; R.L helped writing the manuscript; F.M, V. R, J.O, M.S, R.K, F. R, F.G, V.E, I.L, L.C.A, M.D-A, P.L, C.M, R.M, P.R reviewed the manuscript and participate in the diagnosis/clinical management and C.T had the manuscript idea and reviewed the manuscript.

Corresponding author

Correspondence to Nada Assaf.

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Conflicts of interest

All authors declare that they have no conflict of interest.

Ethical approval

Patient’s informed consent was obtained for anonymous publication of his case. This study has been approved by the ethical committee “Comite ethique recherche clinique” at the centre hospitalier de Versailles, number 21–02.

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Assaf, N., Liévin, R., Merabet, F. et al. KMT2A-ARHGEF12, a therapy related fusion with poor prognosis. Mol Biol Rep 48, 7021–7027 (2021). https://doi.org/10.1007/s11033-021-06621-5

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