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Physiological hypoxia promotes lipid raft and PI3K-dependent activation of MAPK 42/44 in leukemia cells

Leukemia volume 24, pages 1364–1367 (2010)Cite this article

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Recent reports have emphasized the importance of the microenvironment in the development and pathophysiology of malignancies. Although most of these studies investigated interactions between stromal and neoplastic cells, hypoxia has emerged as another component of the microenvironment. Although hypoxia in solid tumors is well studied, it is unclear what role, if any, it has in the physiology of hematologic neoplasias. Lymphomas in this context may resemble solid tumors, but the hypoxic sanctuary for leukemias is thought to be the bone marrow. Hypoxia within the bone marrow of healthy individuals and cancer patients is of additional interest as it may affect hematopoietic progenitors and their differentiation1 as well as bone metastases.

Along with others, we have reported direct measurements of bone marrow pO2 by a simple and minimally invasive method using conventional gas assay methodology routinely used clinically for the measurement of pO2.2, 3 Thus, the average bone marrow pO2 ranged from 48.0 to 54.9 mm Hg. In our previous study, we found that simulation of this physiological hypoxia induces profound changes on the biology of acute myeloid leukemia (AML) cells, in particular expression and function of the chemokine receptor CXCR4, as well as changes in cell signaling, especially in the mitogen-activated protein kinase (MAPK) pathway.3 This notion is of special interest as constitutive activation of the MAPK pathway has been linked to the development of AML4 because of its critical function in proliferation, survival and differentiation, and its prognostic importance in AML.5

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Acknowledgements

We thank Seshagiri Duvvuri, Twee Tsao, Teresa McQueen and Leslie Calvert for technical support. This work was in part supported by a grant from the Deutsche Forschungsgesellschaft (Grant FI 1487 to MF) and supported by grants from the National Cancer Institute (PO1 CA055164, P30 CA016672) and the Paul and Mary Haas Chair in Genetics (to MA).

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Authors and Affiliations

  1. Department of Stem Cell Transplantation and Cellular Therapy, Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Fiegl, I Samudio, Z Mnjoyan, B Korchin & M Andreeff

  2. Department of Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H Fritsche

  3. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Andreeff

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  1. M Fiegl
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  2. I Samudio
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  6. M Andreeff
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Correspondence to M Andreeff.

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Fiegl, M., Samudio, I., Mnjoyan, Z. et al. Physiological hypoxia promotes lipid raft and PI3K-dependent activation of MAPK 42/44 in leukemia cells. Leukemia 24, 1364–1367 (2010). https://doi.org/10.1038/leu.2010.94

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