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Drug Resist Updat. 2009 Aug-Oct;12(4-5):103-13. doi: 10.1016/j.drup.2009.06.001. Epub 2009 Jul 25.

Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches.

Author information

1
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. mkonople@mdanderson.org

Abstract

In hematological malignancies, there are dynamic interactions between leukemic cells and cells of the bone marrow microenvironment. Specific niches within the bone marrow microenvironment provide a sanctuary for subpopulations of leukemic cells to evade chemotherapy-induced death and allow acquisition of a drug-resistant phenotype. This review focuses on molecular and cellular biology of the normal hematopoietic stem cell and the leukemia stem cell niche, and of the molecular pathways critical for microenvironment/leukemia interactions. The key emerging therapeutic targets include chemokine receptors (CXCR4), adhesion molecules (VLA4 and CD44), and hypoxia-related proteins HIF-1alpha and VEGF. Finally, the genetic and epigenetic abnormalities of leukemia-associated stroma will be discussed. This complex interplay provides a rationale for appropriately tailored molecular therapies targeting not only leukemic cells but also their microenvironment to ensure improved outcomes in leukemia.

PMID:
19632887
PMCID:
PMC3640296
DOI:
10.1016/j.drup.2009.06.001
[Indexed for MEDLINE]
Free PMC Article
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