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The influence of hypoxia on CML trafficking through modulation of CXCR4 and E-cadherin expression

Leukemia volume 27, pages 961–964 (2013)Cite this article

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The hematopoietic malignancy, chronic myeloid leukemia (CML) is caused by BCR/ABL, the product of the t(9;22) chromosomal translocation (Deininger et al.1). CML is characterized by abnormal progenitor cell growth and trafficking and premature release of these immature cells into the peripheral blood. Underlying mechanisms include defective adhesion of CML cells to stroma and fibronectin owing to aberrant expression/function of integrins, and in particular, the influence of BCR-ABL on molecules associated with cell adhesion (Wertheim et al.2).

In addition to playing a role in abnormal CML trafficking, stromal cells also contribute to minimal residual disease (MRD) in patients treated with tyrosine kinase inhibitors (TKIs), such as imatinib (Buchdunger et al.3) and nilotinib (Weisberg et al.4). In a recent report (Zhang et al.5), a transgenic mouse model was employed to investigate the influence of the bone marrow (BM) microenvironment on leukemia stem cells with long-term hematopoietic stem cell phenotype in CML. Higher leukemia cell production of G-CSF and lower BM expression of CXCL12 were associated with a decrease in leukemia stem cell homing and withholding of cells in the BM. In addition, aberrant BM expression of cytokines potentiated CML stem cell proliferation yet impaired that of normal stem cells, all of which were partly reversed by imatinib treatment. Disease relapse occurs in more than half of imatinib-treated CML patients (Mahon et al.6). Stromal-derived cytokines that diminish TKI-induced apoptosis have been implicated in MRD that, despite expressing BCR-ABL, is comprised of ABL inhibitor-unresponsive CD34+ cells (Konig et al.7).

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Author notes

  1. A K Azab and E Weisberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Cancer Biology Division, Washington University in Saint Louis School of Medicine, Saint Louis, MO, USA

    A K Azab & F Azab

  2. Deparment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    E Weisberg, I Sahin, J D Griffin & I M Ghobrial

  3. High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, PRC

    F Liu & Q Liu

  4. Department of Pathology, Beth Israel Deaconess Medical Center,

    R Awwad

  5. Harvard Medical School, Boston, MA, USA

    R Awwad

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Correspondence to A K Azab.

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Azab, A., Weisberg, E., Sahin, I. et al. The influence of hypoxia on CML trafficking through modulation of CXCR4 and E-cadherin expression. Leukemia 27, 961–964 (2013). https://doi.org/10.1038/leu.2012.353

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