Tavernier Emmanuelle, Aanei Carmen, Solly Françoise, Flandrin-Gresta Pascale, Campos Lydia, Guyotat Denis
Institut de cancérologie Lucien-Neuwirth, Service d'hématologie, 108 bis, avenue Albert-Raimond, 42270 Saint-Priest-en-Jarez, France, Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France.
CHU Saint-Etienne, Hôpital Nord, laboratoire d'hématologie, 42270 Saint-Priest-en-Jarez, France.
Bull Cancer. 2014 Jun;101(6):593-604. doi: 10.1684/bdc.2014.1925.
CXCR4, receptor of the chemokine SDF-1 (stromal cell-derived factor 1) plays a major role in the normal hematopoiesis but also in the biology of the leukaemic cell. This receptor is expressed on the surface of blasts and is a key molecule in "the anchoring" of the leukaemic stem cell (LSC) within the bone marrow niche. The interactions of the LSC with the bone marrow microenvironment promote survival signals and drug resistance. Recent flow cytometry analyses reported that CXCR4 expression levels have a major prognostic impact in acute myeloid leukaemia (AML). CXCR4 expression is associated with poor prognosis and can be useful to stratify patients, according to their phenotype, in order to establish risk-adapted strategies. Newly diagnosed AML are now routinely stratified according to molecular markers which guide prognosis and treatment. Many leukaemia are composed of multiples subclones with differential susceptibility to treatment and specific targeted therapies are missing. Despite therapeutic improvements for the treatment of AML, long term survival remains poor. Targeting CXCR4 is a novel promising approach of therapy. CXCR4 antagonists are used in combination with chemotherapy in preclinical and clinical studies. This review summarises our current knowledge regarding the key role of CXCR4 in AML and discusses how targeting this pathway could provide an interesting approach to eradicate the LSC.
趋化因子SDF-1（基质细胞衍生因子1）的受体CXCR4在正常造血过程中发挥着重要作用，在白血病细胞生物学中也同样如此。该受体在原始细胞表面表达，是白血病干细胞（LSC）在骨髓龛内“锚定”的关键分子。LSC与骨髓微环境的相互作用促进生存信号和耐药性。最近的流式细胞术分析报告称，CXCR4表达水平对急性髓系白血病（AML）具有重要的预后影响。CXCR4表达与预后不良相关，根据患者表型对其进行分层可能有助于制定风险适应性策略。新诊断的AML现在通常根据指导预后和治疗的分子标志物进行分层。许多白血病由多个对治疗敏感性不同的亚克隆组成，且缺乏特定的靶向治疗方法。尽管AML的治疗有了改善，但长期生存率仍然很低。靶向CXCR4是一种很有前景的新型治疗方法。在临床前和临床研究中，CXCR4拮抗剂与化疗联合使用。本综述总结了我们目前关于CXCR4在AML中的关键作用的知识，并讨论了靶向该途径如何能为根除LSC提供一种有趣的方法。
