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Chronic myelogenous leukemia

Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia

Leukemia volume 34, pages 2230–2233 (2020)Cite this article

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The Philadelphia (Ph) chromosome is the most common cytogenetic abnormality in adults diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occurring in about 30–40% of all cases [1]. The Ph chromosome results from the reciprocal translocation of ABL1 gene located at 9q34 with BCR gene at 22q11, resulting in the BCR-ABL1 fusion gene that encodes the BCR-ABL1 oncoprotein with constitutively activated tyrosine kinase activity [2]. The BCR-ABL1 fusion gene is considered as a founding event in ALL pathogenesis defining key features of the disease. The addition of a tyrosine kinase inhibitor (TKI) to chemotherapy with allogeneic hematopoietic stem cell transplantation (alloHSCT) in first remission has significantly improved outcome in this particular ALL subtype [3]. However, Ph-positive ALL retains a poor prognosis with a high relapse rate compared to other BCP-ALL subtypes. Importantly, resistances to TKIs have been described and may contribute to disease escape and subsequent relapse. We report here the case of an adult patient with a Ph-positive ALL who relapsed after the selective loss of the Ph chromosome following chemotherapy, TKI exposure and alloHSCT. Cytogenetic and molecular analyses confirmed the loss of the BCR-ABL1 fusion with persistence of the ABL1-BCR juxtaposition, and demonstrated the clonal relationship between diagnosis and relapse.

The study was conducted according to the Declaration of Helsinki and was approved by the Human Research Committee of Lille and the internal review board of the Lille University Hospital Tumor Bank (certification NF 96900-2014/65453-1) after the patient’s consent.

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Fig. 1: Cytogenetic analyses.
Fig. 2: Molecular MRD monitoring during disease course.

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Acknowledgements

We thank Christophe Roumier (Tumour Bank, certification NF 96900-2014/65453-1, Centre Hospitalier Universitaire de Lille) for handling, conditioning, and storing patient samples.

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Author notes

  1. These authors contributed equally: Nicolas Gazeau, Coralie Derrieux

Authors and Affiliations

  1. CHU Lille, Hematology Department, Claude Huriez Hospital, F-59000, Lille, France

    Nicolas Gazeau, Céline Berthon, Laure Goursaud, Valérie Coiteux & Bruno Quesnel

  2. CHU Lille, Laboratory of Hematology, F-59000, Lille, France

    Coralie Derrieux, Olivier Nibourel, Nathalie Grardel, Thomas Boyer, Florent Dumezy, Claude Preudhomme & Nicolas Duployez

  3. University of Lille, INSERM, UMR-S 1172, F-59000, Lille, France

    Olivier Nibourel, Céline Berthon, Thomas Boyer, Bruno Quesnel, Claude Preudhomme, Catherine Roche-Lestienne & Nicolas Duployez

  4. CHU Lille, Institute of Medical Genetics, Jeanne de Flandre Hospital, F-59000, Lille, France

    Catherine Roche-Lestienne

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  1. Nicolas Gazeau
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Contributions

NGa, CD and ND collected data and drafted the paper. TB and FD performed flow cytometry. CD, NGr, ON, CP and ND acquired and analyzed molecular data. CRL acquired and analyzed cytogenetical data. CB, LG, VC and BQ provided samples and clinical data. All authors critically revised the paper and approved the final version.

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Correspondence to Nicolas Duployez.

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Gazeau, N., Derrieux, C., Nibourel, O. et al. Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia. Leukemia 34, 2230–2233 (2020). https://doi.org/10.1038/s41375-020-0715-2

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