| Autor: |
Hui Zhang, Fei Yu, Yingshi Chen, Mo Zhou, Jing-Wen Zhang, Lingling Liu, Bingfeng Liu, Jun Liu, Ting Pan, Yuewen Luo, Xu Zhang, Hailan Ou, Wenjing Huang, Xi Lv, Zhihui Xi, Ruozhi Xiao, Lixue Cao, Lijuan Lu, Xiancai Ma |
| Rok vydání: |
2023 |
| Popis: |
Acute myeloid leukemia (AML) is caused by clonal disorders of hematopoietic stem cells. Differentiation therapy is emerging as an important treatment modality for leukemia, given its less toxicity and wider applicable population, but the arsenal of differentiation-inducing agents is still very limited. In this study, we adapted a competitive peptide phage display platform to search for candidate peptides that could functionally induce human leukemia cell differentiation. A monoclonal phage (P6) and the corresponding peptide (pep-P6) was identified. Both L- and D-chirality of pep-P6 showed potent efficiency in inducing THP-1 cells differentiation, driving their morphologic maturation and upregulating the expression of macrophage markers and cytokines including CD11b, CD14, IL-6, IL-1β and TNF-α. In the THP-1 xenograft animal model, administration of D-pep-P6 was effective in inhibiting tumor growth. Importantly, exposure to D-pep-P6 induced the differentiation of primary human leukemia cells isolated AML patients in a similar manner to the THP-1 cells. Further mechanical study suggested that D-pep-P6 induced human leukemia cell differentiation by directly activating a TLR-2 signaling pathway. These findings identify a novel D-peptide that may promote leukemia differentiation therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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