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BCR-ABLT315I transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge?

Leukemia volume 21, pages 2204–2206 (2007)Cite this article

The Abl tyrosine kinase inhibitor imatinib mesylate (IM) now represents the new standard treatment of chronic myeloid leukemia (CML).1 However, a growing number of CML patients develop imatinib resistance and several mechanisms of resistance have been described, including BCR-ABL mutations. While most mutant forms are sensitive to new second-generation tyrosine kinase inhibitors (TKIs) (dasatinib and nilotinib), the T315I mutation remains completely refractory to imatinib, as well as to these new agents.2

Homoharringtonine (HHT), a cephalotaxine ester that has demonstrated a clinical activity in myeloproliferative diseases,3, 4 inhibits protein synthesis and induces cell differentiation and apoptosis. The absence of cross-resistance between HHT and IM in imatinib-resistant leukemic cell lines has been demonstrated, and even a possible synergy between the two compounds has been observed in vitro. HHT decreases the production of the oncogenic kinase BCR-ABL, by inhibition of transcription and translation in the same way in BCR-ABLT315I mutant and in wild-type cell lines.

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Author notes

  1. L Legros and S Hayette: These authors contributed equally to this work

Authors and Affiliations

  1. Hematology Department, Hôpital Archet 1, Nice, France

    L Legros & J-P Cassuto

  2. Laboratory for Cytogenetics and Molecular Biology and EA3737, Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    S Hayette, K Chabane & J-P Magaud

  3. Hematology Department, Hôpital Edouard Herriot, Lyon, France

    F E Nicolini

  4. Hematology Laboratory, Hôpital Pasteur, Nice, France

    S Raynaud

  5. Hematology Department, Hôpital Edouard Herriot, Lyon, France

    M Michallet

Authors
  1. L Legros
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  2. S Hayette
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  3. F E Nicolini
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  4. S Raynaud
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  5. K Chabane
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  6. J-P Magaud
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  7. J-P Cassuto
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  8. M Michallet
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Correspondence to L Legros.

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Legros, L., Hayette, S., Nicolini, F. et al. BCR-ABLT315I transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge?. Leukemia 21, 2204–2206 (2007). https://doi.org/10.1038/sj.leu.2404772

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