Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sci Transl Med. 2017 Jan 25;9(374). doi: 10.1126/scitranslmed.aaj2025.
Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by self-renewing malignant stem cells; thus, eradication of AML and MDS stem cells is required for cure. We identified CD99 as a cell surface protein frequently overexpressed on AML and MDS stem cells. Expression of CD99 allows for prospective separation of leukemic stem cells (LSCs) from functionally normal hematopoietic stem cells in AML, and high CD99 expression on AML blasts enriches for functional LSCs as demonstrated by limiting dilution xenotransplant studies. Monoclonal antibodies (mAbs) targeting CD99 induce the death of AML and MDS cells in a SARC family kinase-dependent manner in the absence of immune effector cells or complement, and anti-CD99 mAbs exhibit antileukemic activity in AML xenografts. These data establish CD99 as a marker of AML and MDS stem cells, as well as a promising therapeutic target in these disorders.
急性髓细胞白血病 (AML) 和骨髓增生异常综合征 (MDS) 是由自我更新的恶性干细胞引发和维持的；因此，治愈 AML 和 MDS 需要消除干细胞。我们发现 CD99 是 AML 和 MDS 干细胞表面经常过度表达的一种细胞表面蛋白。CD99 的表达允许在 AML 中从功能正常的造血干细胞中前瞻性分离白血病干细胞 (LSCs)，并且 AML 原始细胞上的高 CD99 表达通过限制稀释异种移植研究富集功能性 LSCs。针对 CD99 的单克隆抗体 (mAb) 在没有免疫效应细胞或补体的情况下以 SARC 家族激酶依赖性方式诱导 AML 和 MDS 细胞死亡，并且抗 CD99 mAb 在 AML 异种移植物中具有抗白血病活性。这些数据将 CD99 确立为 AML 和 MDS 干细胞的标志物，以及这些疾病中很有前途的治疗靶点。
