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A novel role for the marrow microenvironment in initiating and sustaining hematopoietic disease

Journal

EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 9, Issue 1, Pages 21-28

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1517/14712590802603093

Keywords

hematological malignancy; hematopoesis; marrow microenvironment; stromal cells

Funding

  1. NIH [HL03644, HL082941]
  2. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL036444, R01HL082941] Funding Source: NIH RePORTER

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Background: The marrow microenvironment is composed of a complex network of cells and extra cellular matrix that cooperate to regulate normal hematopoiesis. There is growing evidence that microenvironmental defects can contribute to the pathogenesis of hematological malignancies. Objective/methods: We review the role of the microenvironment in inducing and sustaining hematological malignancies. Results/conclusions: Two basic mechanisms could explain the role of microenvironmental defects in the evolution of hematopoietic neoplasms. There is significant data to support the first mechanism, in which the malignant hematopoietic clone induces reversible functional changes in the microenvironment that result in improved growth conditions for the malignant cells. More recent studies from mouse models have indicated that a second mechanism involving primary microenvironmental defects can also result in malignancy.

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