State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC), PR China.
Cancer Lett. 2010 Oct 1;296(1):65-73. doi: 10.1016/j.canlet.2010.03.021. Epub 2010 May 4.
Acute myeloid leukemia (AML) arises from genetic changes at the level of stem cell, various mutations have been elucidated, including AML1-ETO fusion gene has been shown as the representative target of cellular transformation for LSCs originating from hematopoietic stem cells (HSCs) compartment. LSCs resemble HSCs with respect to self-renewal capacity and chemotherapy-resistance. However, LSCs possess specific cell-surface markers, they are proposed to reside within the CD34(+)/CD38(-)/CD123(+) compartment. And the interaction mediated by adhesion molecules between LSCs and niche played a role in chemoresistance of LSCs. Therefore, study on the LSCs surface makers related to niche is helpful for the potential target therapy in the future. In this study, the proportions of CD34(+)/CD38(-)/CD123(+) LSCs compartment co-expressing the three adhesion molecules, N-Cadherin, Tie2 and CD44, respectively, from AML patients before and after chemotherapy were analyzed. We demonstrated N-Cadherin and Tie2 positive CD34(+)/CD38(-)/CD123(+) LSCs populations could be enriched by chemotherapy. Furthermore, AML1/ETO fusion signals and MDR1 expression were detected on the CD34(+)/CD38(-)/CD123(+) LSCs populations expressing N-Cadherin and Tie2. Therefore, N-Cadherin and Tie2 are probably the potential markers for identification of LSCs.
急性髓细胞白血病 (AML) 源于干细胞水平的遗传改变,已经阐明了各种突变,包括 AML1-ETO 融合基因已被证明是源自造血干细胞 (HSCs) 隔室的 LSCs 细胞转化的代表性靶标。LSCs 在自我更新能力和化疗耐药性方面与 HSCs 相似。然而,LSCs 具有特定的细胞表面标记物,它们被认为存在于 CD34(+)/CD38(-)/CD123(+) 隔室中。并且 LSCs 与龛之间由粘附分子介导的相互作用在 LSCs 的化疗耐药性中起作用。因此,研究与龛相关的 LSCs 表面标志物有助于未来的潜在靶向治疗。在这项研究中,分析了化疗前后 AML 患者中分别共表达三种粘附分子 N-钙粘蛋白、Tie2 和 CD44 的 CD34(+)/CD38(-)/CD123(+) LSCs 隔室的比例。我们证明 N-钙粘蛋白和 Tie2 阳性 CD34(+)/CD38(-)/CD123(+) LSCs 群体可以通过化疗富集。此外,在表达 N-钙粘蛋白和 Tie2 的 CD34(+)/CD38(-)/CD123(+) LSCs 群体上检测到 AML1/ETO 融合信号和 MDR1 表达。因此,N-钙粘蛋白和 Tie2 可能是鉴定 LSCs 的潜在标志物。