白血病微环境相互作用的治疗靶点：机制与方法。
Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches.
机构信息
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Drug Resist Updat. 2009 Aug-Oct;12(4-5):103-13. doi: 10.1016/j.drup.2009.06.001. Epub 2009 Jul 25.
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.
摘要
在血液恶性肿瘤中，白血病细胞与骨髓微环境细胞之间存在动态相互作用。骨髓微环境中的特定龛位为白血病细胞的亚群提供了避难所，使其能够逃避化疗诱导的死亡，并获得耐药表型。本综述重点介绍正常造血干细胞和白血病干细胞龛位的分子和细胞生物学，以及对微环境/白血病相互作用至关重要的分子途径。新兴的关键治疗靶点包括趋化因子受体（CXCR4）、黏附分子（VLA4 和 CD44）以及与缺氧相关的蛋白 HIF-1alpha 和 VEGF。最后，将讨论与白血病相关的基质的遗传和表观遗传异常。这种复杂的相互作用为靶向不仅针对白血病细胞而且针对其微环境的分子治疗提供了依据，以确保在白血病中获得更好的结果。
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