Saint Vincent's Comprehensive Cancer Center, New York, NY, USA.
J Hematol Oncol. 2008 Jul 10;1:8. doi: 10.1186/1756-8722-1-8.
In a departure from conventional strategies to improve treatment outcome for myeloid malignancies, we report the isolation of leukemia-specific peptides using a phage display library screened with freshly obtained human myeloid leukemia cells.
A phage display library was screened by 5 rounds of biopanning with freshly isolated human AML cells. Individual colonies were randomly picked and after purification, biologic activity (growth and differentiation) on fresh AML cells was profiled. Ten peptides were synthesized for further biological studies. Multiple peptides were found to selectively bind to acute myeloid leukemia (AML) cells. The peptides bound to leukemia cells, were internalized and could induce proliferation and/or differentiation in the target patient cells. Two of the peptides, HP-A2 and HP-G7, appeared to have a novel mechanism of inducing differentiation since they did not cause G1 arrest in cycling cells even as the expression of the differentiation marker CD11b increased.
Peptide induced differentiation of leukemia cells offers a novel treatment strategy for myeloid malignancies, whereas their ability to induce proliferation could be harnessed to make cells more sensitive to chemotherapy. Conceptually, these leukemia specific peptides can also be used to refine diagnosis, document minimal residual disease, and selectively deliver toxins to malignant cells.
与传统改善髓系恶性肿瘤治疗效果的策略不同，我们报告了使用经过新鲜获得的人髓系白血病细胞筛选的噬菌体展示文库分离白血病特异性肽。
通过用新鲜分离的人 AML 细胞进行 5 轮生物淘选，对噬菌体展示文库进行了筛选。随机挑选单个菌落，经纯化后，对新鲜 AML 细胞上的生物学活性（生长和分化）进行了分析。为进一步的生物学研究合成了 10 个肽。发现多个肽选择性地结合急性髓系白血病 (AML) 细胞。这些肽与白血病细胞结合，被内化，并能在靶标患者细胞中诱导增殖和/或分化。两种肽，HP-A2 和 HP-G7，似乎具有诱导分化的新机制，因为它们不会导致细胞周期中 G1 期停滞，即使分化标志物 CD11b 的表达增加。
肽诱导白血病细胞分化为髓系恶性肿瘤提供了一种新的治疗策略，而其诱导增殖的能力可用于使细胞对化疗更敏感。从概念上讲，这些白血病特异性肽也可用于改进诊断、记录微小残留疾病，并选择性地将毒素递送至恶性细胞。
