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Clonal history of a cord blood donor cell leukemia with prenatal somatic JAK2 V617F mutation

Leukemia volume 30, pages 1756–1759 (2016)Cite this article

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Donor cell-derived leukemia is an uncommon complication after cord blood (CB) transplantation, and has been suggested to result from the evolution of a pre-leukemic clone existing in the CB.1 Here, we report a case of a CB-derived leukemia (CBDL) and describe the clonal history of the disease.

Twenty months after transplantation, the patient presented with hepato-splenomegaly and nodular skin lesions. Cell blood counts and blood smear examination retrieved anemia, thrombocytopenia and 24.6 × 109 per liter leukocytes with 40% of large myeloid blasts. The medullar analysis showed 69% of CD34− HLADR− CD33+ CD13+ CD117+ MPO− CD36+ CD7+ blast infiltration (Figures 1a and b), with a 48,XY,+6,der(13)t(13;?)(p11;?),+21[12]/46,XY[3] karyotype. As clinical, morphologic, immunophenotypic and karyotypic presentations at relapse were different from those at diagnosis, the hypothesis of donor cell leukemia was envisioned. Chimerism analysis confirmed this hypothesis by retrieving 99% of donor cells in blood samples, indicating that the second leukemia arose from donor cells.

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Acknowledgements

This project was funded by the Fondation ARC pour la Recherche sur le Cancer (N°EML20110602421), by the Région Ile-de-France (N°2012-2-eml-06-UPMC_12016710), by the Association Laurette Fugain (N°J15I409) and by the Institut National du Cancer (INCA) (PH).

Author contributions

PH performed the cell culture, genotyping and next-generation sequencing (NGS) experiments, interpreted the results and wrote the manuscript. ACM and SL collected clinical data and contributed in follow-up of the patient. RB coordinated HSC transplantation and contributed in the material collection. RT designed NGS assays. LS performed cytological and flow cytometry analysis of patient samples. DB and CM performed the standard molecular and chimerism analysis. FF contributed in the material collection and sample preparation. MM and OL contributed in the follow-up of the patient. FD designed the research, interpreted the results and wrote the manuscript. All authors contributed in manuscript review.

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Authors and Affiliations

  1. Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France

    P Hirsch, A C Mamez, L Suner, O Legrand, M Mohty, L Douay & F Delhommeau

  2. INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    P Hirsch, L Suner, O Legrand, M Mohty, L Douay & F Delhommeau

  3. Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC, Paris, France

    P Hirsch, S Lapusan, L Suner, O Legrand, M Mohty, L Douay & F Delhommeau

  4. AP-HP, Hôpital Saint-Antoine, Service d'Hématologie clinique et de thérapie cellulaire, Paris, France

    P Hirsch, A C Mamez, R Belhocine, S Lapusan, R Tang, F Fava, O Legrand & M Mohty

  5. AP-HP, Hôpital Saint-Antoine & Hôpital Armand-Trousseau, Service d’hématologie biologique, Paris, France

    L Suner, C Marzac, L Douay & F Delhommeau

  6. AP-HP, Hôpital Henri Mondor, Unité d'Hématologie Moléculaire, Créteil, France

    D Bories

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  1. P Hirsch
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  8. C Marzac
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Corresponding author

Correspondence to F Delhommeau.

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The authors declare no conflict of interest.

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Hirsch, P., Mamez, A., Belhocine, R. et al. Clonal history of a cord blood donor cell leukemia with prenatal somatic JAK2 V617F mutation. Leukemia 30, 1756–1759 (2016). https://doi.org/10.1038/leu.2016.31

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