Cao Tingyong, Ye Yuanxin, Liao Hongyan, Shuai Xiao, Jin Yongmei, Su Jun, Zheng Qin
Department of Hematology.
Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
Medicine (Baltimore). 2019 Jun;98(23):e15948. doi: 10.1097/MD.0000000000015948.
CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.
CXC趋化因子受体4（CXCR4）在急性髓系白血病（AML）细胞上的表达与基质细胞衍生因子-1α（SDF-1α）相关，并使造血祖细胞和白血病细胞保留在骨髓微环境中。在此，我们通过流式细胞术检测了134例初发AML患者和21例对照者的CXCR4表达，评估了CXCR4表达与临床特征之间的关系，并前瞻性地阐明了CXCR4表达在AML中的预后意义。我们发现AML患者的CXCR4表达明显高于对照者（P = 0.000）。根据CXCR4相对荧光强度（RFI）的中位数，将134例初发AML患者分为2组。在接受化疗的106例AML患者中，CXCR4高表达组（RFI>4.23）的总生存期（OS）和无病生存期（DFS）明显短于CXCR4低表达组（RFI≤4.23）（分别为P = 0.002；0.026）。此外，在接受诱导治疗的87例非M3患者中，CXCR4高表达组的OS有显著下降，但DFS无显著下降（分别为P = 0.047和0.178）。此外，在化疗后达到完全缓解（CR）的所有AML患者和非M3患者中，高水平的CXCR4表达均独立增加了复发风险（优势比分别为1.090，P = 0.010；优势比为1.068，P = 0.048）。总体而言，我们的数据表明，CXCR4过表达是所有AML患者和非M3患者疾病复发和较差OS的独立预后因素。CXCR4表达水平可在疾病初发时通过快速简便的流式细胞术测定。因此，CXCR4可作为预后不良的AML患者的潜在治疗靶点。
