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Evidence for D276G and L364I Bcr-Abl mutations in Ph+ leukaemic cells obtained from patients resistant to Imatinib

Leukemia volume 19, pages 132–134 (2005)Cite this article

TO THE EDITOR

In this report, we present our experience with 20 patients affected by chronic myelogenous leukaemia (CML) in blast crisis (BC)/accelerated phase (AP) or by Ph+ acute lymphoblastic leukaemia (ALL) treated with Imatinib and in whom resistance to the drug (defined as the inability to maintain a haematological response or as the progression to BC for patients who were in AP at the start of the treatment) developed. These patients were enrolled in registrative or not registrative trials of Imatinib as monotherapy. The results obtained are reported here.

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References

  1. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876–880.

    Article  CAS  Google Scholar 

  2. Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW et al. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing Imatinib mesylate-resistant Bcr-Abl kinases. Blood 2003; 101: 664–672.

    Article  CAS  Google Scholar 

  3. Azam M, Latek RR, Daley GQ . Mechanisms of autoinhibition and STI-571/Imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 2003; 112: 831–843.

    Article  CAS  Google Scholar 

  4. Al-Ali HK, Heinrich MC, Lange T, Krahl R, Mueller M, Muller C et al. High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to Imatinib. Hematol J 2004; 5: 55–60.

    Article  CAS  Google Scholar 

  5. Gambacorti-Passerini CB, Gunby RH, Piazza R, Galietta A, Rostagno R, Scapozza L . Molecular mechanisms of resistance to Imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol 2003; 4: 75–85.

    Article  Google Scholar 

  6. Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T et al. Molecular and chromosomal mechanisms of resistance to Imatinib (STI571) therapy. Leukemia 2002; 16: 2190–2196.

    Article  CAS  Google Scholar 

  7. Gambacorti-Passerini C, Zucchetti M, Russo D, Frapolli R, Verga M, Bungaro S et al. Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin Cancer Res 2003; 9: 625–632.

    CAS  PubMed  Google Scholar 

  8. Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 2003; 102: 276–283.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Oncology, National Cancer Institute, Milan, Italy

    R G Piazza, V Magistroni, F Andreoni, A Galietta & C Gambacorti-Passerini

  2. University of Milano Bicocca, S Gerardo Hospital, Monza

    R G Piazza

  3. Department of Chemistry and Applied BioSciences at the Swiss Federal Institute of Technology, Zurich, Switzerland

    M Gasser & L Scapozza

  4. Department of Internal Medicine, Section of Hematology, University of Milano Bicocca, San Gerardo Hospital, Monza

    C Gambacorti-Passerini

Authors
  1. R G Piazza
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  2. V Magistroni
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  3. M Gasser
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  4. F Andreoni
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  5. A Galietta
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  6. L Scapozza
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  7. C Gambacorti-Passerini
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Corresponding author

Correspondence to C Gambacorti-Passerini.

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Piazza, R., Magistroni, V., Gasser, M. et al. Evidence for D276G and L364I Bcr-Abl mutations in Ph+ leukaemic cells obtained from patients resistant to Imatinib. Leukemia 19, 132–134 (2005). https://doi.org/10.1038/sj.leu.2403453

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  • DOI: https://doi.org/10.1038/sj.leu.2403453

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