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Chronic Myeloproliferative Neoplasias

BCR and BCR-ABL regulation during myeloid differentiation in healthy donors and in chronic phase/blast crisis CML patients

Leukemia volume 24, pages 1445–1449 (2010)Cite this article

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Abstract

Chronic myeloid leukemia (CML) is caused by the BCR-ABL hybrid gene. The molecular mechanisms leading from chronic phase (CP) to blast crisis (BC) are not understood. However, both the presence and the levels of BCR-ABL seem to be important for CML progression. BCR-ABL is under the transcriptional control of BCR promoter. Here we focused on the gene expression control of BCR and BCR-ABL upon myeloid differentiation in healthy donors (HDs), CP and BC patients. As previously reported, BCR-ABL is downregulated during myeloid maturation in CP patients. A similar pattern was detected for BCR (but not for ABL) in CP-CML and in HD, thus suggesting that the two genes may be under a similar transcriptional control. In BC this mechanism is similarly impaired for both BCR-ABL and BCR. These data indicate the presence of an ‘in trans’ deregulated transcription of both BCR and BCR-ABL promoters, associated with CML progression.

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Acknowledgements

We thank Dr Cristina Bugarin and Dr Giuseppe Gaipa from Tettamanti Foundation for flow cytometry analysis. This study was supported by Italian Association for Cancer Research, AIRC IG-4637 2007-2009 ‘Targeting oncogenic fusion genes: from CML to prostate’, PRIN 2007 ‘Patogenesi e terapia molecolare della progressione neoplastica nella leucemia mieloide cronica’, PRIN 2007 ‘Patogenesi e terapia molecolare della progressione neoplastica nella leucemia mieloide cronica’ and Ministero dell'Istruzione, dell'Università e della Ricerca, Regione Lombardia-Farmacovigilanza. MM performed the experiments and wrote the first draft of the paper; RGP designed the experiment and helped in writing the paper; CGP supervised work and wrote the final version of the paper; AP, IM, II, AM, SR and MP processed and collected the samples; EMP supervised work.

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  1. M Marega and R G Piazza: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Medicine, University of Milano-Bicocca, Monza, Italy

    M Marega, R G Piazza, A Pirola, S Redaelli, A Mogavero, E M Pogliani & C Gambacorti-Passerini

  2. Institute of Hematology and Medical Oncology, ‘L and A Seràgnoli’ S Orsola Malpighi Hospital, University of Bologna, Bologna, Italy

    I Iacobucci

  3. Division of Clinical Hematology, San Gerardo de' Tintori Hospital, University of Milano-Bicocca, Monza, Italy

    I Meneghetti, M Parma, E M Pogliani & C Gambacorti-Passerini

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  1. M Marega
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  2. R G Piazza
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  3. A Pirola
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  4. S Redaelli
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  8. M Parma
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  10. C Gambacorti-Passerini
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Correspondence to C Gambacorti-Passerini.

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Marega, M., Piazza, R., Pirola, A. et al. BCR and BCR-ABL regulation during myeloid differentiation in healthy donors and in chronic phase/blast crisis CML patients. Leukemia 24, 1445–1449 (2010). https://doi.org/10.1038/leu.2010.101

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