Targeting the CXCL12/CXCR4 axis in acute myeloid leukemia: from bench to bedside

被引:76
作者
Cho, Byung-Sik [1 ,2 ]
Kim, Hee-Je [1 ]
Konopleva, Marina [2 ]
机构
[1] Catholic Univ Korea, Dept Hematol, Catholic Blood & Marrow Transplantat Ctr, Seoul St Marys Hosp,Leukemia Res Inst,Coll Med, Seoul, South Korea
[2] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Sect Mol Hematol & Therapy, 1515 Holcombe Blvd,Unit 0448, Houston, TX 77030 USA
基金
新加坡国家研究基金会;
关键词
Leukemia; myeloid; acute; CXCR4; CXCL12; HEMATOPOIETIC STEM; CXCR4; EXPRESSION; CELLS; MOBILIZATION; SURVIVAL; CHEMOSENSITIZATION; CHEMOTHERAPY; PROGENITORS; PLERIXAFOR; ACTIVATION;
D O I
10.3904/kjim.2016.244
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The interactions between the cancerous cells of acute myeloid leukemia (AML) and the bone marrow (BM) microenvironment have been postulated to be important for resistance to chemotherapy and disease relapse in AML. The chemokine receptor CXC chemokine receptor 4(CXCR4) and its ligand, CXC motif ligand 12(CXCL12), also known as stromal cell-derived factor 1a, are key mediators of this interaction. CXCL12 is produced by the BM microenvironment, binds and activates its cognate receptor CXCR4 on leukemic cells, facilitates leukemia cell trafficking and homing in the BM microenvironment, and keeps leukemic cells in close contact with the stromal cells and extracellular matrix that constitutively generate growth-promoting and anti-apoptotic signals. Indeed, a high level of CXCR4 expression on AML blasts is known to be associated with poor prognosis. Recent preclinical and clinical studies have revealed the safety and potential clinical utility of targeting the CXCL12/CXCR4 axis in AML with different classes of drugs, including small molecules, peptides, and monoclonal antibodies. In this review, we describe recent evidence of targeting these leukemia-stroma interactions, focusing on the CXCL12/CXCR4 axis. Related early phase clinical studies will be also introduced.
引用
收藏
页码:248 / 257
页数:10
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