Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Sweden
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Sweden.
Haematologica. 2018 Mar;103(3):447-455. doi: 10.3324/haematol.2017.169946. Epub 2017 Dec 28.
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34CD38) and progenitor (CD34 CD38) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 antibody.
酪氨酸激酶抑制剂（TKIs）在治疗慢性髓性白血病（CML）方面非常有效，但很少有患者被治愈。TKI 的主要缺点是它们在消除负责疾病维持和停药后复发的白血病干细胞方面效果不佳。在此，我们对经流式分选的原始（CD34 CD38）和祖细胞（CD34 CD38）慢性期 CML 细胞进行了核糖核酸测序，并发现相对于相应的正常骨髓细胞，有 32 个细胞表面分子的转录水平上调。我们专注于原始 CML 细胞中表达上调的新型标志物，通过流式细胞术证实了清道夫受体 CD36 和瘦素受体的上调。我们还描绘了一个表达 CD36 的原始 CML 细胞亚群，该亚群对伊马替尼治疗的敏感性降低。使用 CD36 靶向抗体，我们表明 CD36 阳性细胞可以通过抗体依赖性细胞毒性被靶向和杀死。总之，CD36 定义了一个原始 CML 细胞亚群，其伊马替尼敏感性降低，可以使用抗 CD36 抗体有效地靶向和杀死。
