ArticleMicrobial cell factories2021
Expression of a recombinant FLT3 ligand and its emtansine conjugate as a therapeutic candidate against acute myeloid leukemia cells with FLT3 expression.
Article in Microbial cell factories, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Ultrasensitive Detection of Rare Mutations via Amplifying-Cleaving-Enriching in Acute Myeloid Leukemia.Biomedicines · 2025Article
- FLT3L-based drug conjugate effectively targets chemoresistant leukemia stem cells in acute myeloid leukemia.Cell reports. Medicine · 2025Article
- miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.Cell death discovery · 2023Article
- Efficacy of SCF drug conjugate targeting c-KIT in gastrointestinal stromal tumor.BMC medicine · 2022Article
- Nickel (II) and Cobalt (II) Alginate Biopolymers as a "Carry and Release" Platform for Polyhistidine-Tagged Proteins.Gels (Basel, Switzerland) · 2022Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMost patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30-40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML. Here, E. coli was used as a host to express recombinant human FLT3 ligand (rhFL), which was used as a specific vehicle to deliver cytotoxic drugs to FLT3 + AML cells.
methodsRecombinant hFL was expressed and purified from induced recombinant BL21 (DE3) E. coli. Purified rhFL and emtansine (DM1) were conjugated by an N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) linker. We evaluated the potency of the conjugation product FL-DM1 against FLT3-expressing AML cells by examining viability, apoptosis and the cell cycle. The activation of proteins related to the activation of FLT3 signaling and apoptosis pathways was detected by immunoblotting. The selectivity of FL-DM1 was assessed in our unique HCD-57 cell line, which was transformed with the FLT3 internal tandem duplication mutant (FLT3-ITD).
resultsSoluble rhFL was successfully expressed in the periplasm of recombinant E. coli. The purified rhFL was bioactive in stimulating FLT3 signaling in AML cells, and the drug conjugate FL-DM1 showed activity in cell signaling and internalization. FL-DM1 was effective in inhibiting the survival of FLT3-expressing THP-1 and MV-4-11 AML cells, with half maximal inhibitory concentration (IC
conclusionsOur data demonstrated that soluble rhFL can be produced in a bioactive form in the periplasm of recombinant E. coli. FL can be used as a specific vehicle to deliver DM1 into FLT3-expressing AML cells. FL-DM1 exhibited cytotoxicity in FLT3-expressing AML cell lines and primary AML cells. FL-DM1 may have potential clinical applications in treating patients with FLT3-positive AML.
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