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-1α 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.
Original language | English (US) |
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Pages (from-to) | 103-113 |
Number of pages | 11 |
Journal | Drug Resistance Updates |
Volume | 12 |
Issue number | 4-5 |
DOIs | |
State | Published - Aug 2009 |
Keywords
- AMD3100
- Bone marrow microenvironment
- CXCR4
- Drug resistance
- Leukemia
- Molecular targeted therapy
- Stem cell niche
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Cancer Research
- Infectious Diseases
- Pharmacology (medical)