Research press release


Nature Medicine

Mobilizing hematopoietic stem cells



H Geigerたちは、EGFRがG-CSFによるHSCの動員を妨げる働きをすることを明らかにした。Geigerたちはマウスで研究を行い、HSCのEGFR発現を抑制すると、G-CSFに依存した動員が促進されることを発見した。重要なのは、EGFRを標的とする薬で数種類のがんの治療に利用されるエルロチニブを用いても同様な動員促進作用がみられることで、この発見が臨床的に重要な意味をもつことがわかる。

Inhibition of the epidermal growth factor receptor (EGFR) on cell surfaces promotes the mobilization of hematopoietic stem cells (HSCs) — which give rise to all types of blood cells. As EGFR is the target of drugs already in clinical use, this finding, reported in this week’s Nature Medicine, may have direct implications for the treatment of diseases that require HSC transplants.

Patients with a series of blood disorders, including certain cancers, often need to receive HSC transplants. Harvesting these cells in amounts sufficient for transplantation is challenging, as HSCs are rare and reside in the bone marrow. To reduce risks to donors, the common procedure for harvesting HSC is to induce the cells to mobilize from the bone marrow into the peripheral blood. A protein known as granulocyte colony-stimulating factor (G-CSF) is commonly used to induce this mobilization, but the results with this molecule are not optimal, and there is a need for more successful methods to promote HSCs mobilization.

Hartmut Geiger and his colleagues now report that EGFR acts to counter HSC mobilization by G-CSF. Working in mice, the team found that reducing EGFR expression in HSCs increased G-CSF-dependent mobilization. Crucially, the use of erlotinib, a drug that targets EGFR and is used to treat several forms of cancer, had the same mobilization-promoting activity, underscoring the clinical implications of this discovery.

doi: 10.1038/nm.2217


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