Fms-related tyrosine kinase 3 ligand (FLT3L) (FLT3L)

Fms-related tyrosine kinase 3 ligand (FLT3L) is a hematopoietic cytokine that plays a pivotal role in the immune system by promoting the proliferation and differentiation of hematopoietic stem cells and progenitor cells. It is particularly essential for the development of dendritic cells (DCs), including conventional and plasmacytoid subtypes, which are critical for antigen presentation and the initiation of adaptive immune responses (UniProt P49771, PubMed: 28219922). FLT3L exerts its biological effects by binding to the FLT3 receptor (CD135), a class III receptor tyrosine kinase. In clinical oncology, recombinant FLT3L (e.g., CDX-301) is utilized as an immunotherapeutic agent to expand DC populations and enhance the efficacy of cancer vaccines and checkpoint inhibitors (ClinicalTrials.gov: NCT02129075). Conversely, in hematologic malignancies like acute myeloid leukemia (AML), FLT3L levels often increase following chemotherapy, which can inadvertently support the survival and regrowth of FLT3-mutated leukemic blasts, presenting a challenge for receptor-targeted therapies (PubMed: 23550014). Beyond oncology, the FLT3L signaling pathway is also investigated as a target in autoimmune diseases, where neutralizing the ligand may help reduce aberrant immune activation.

Other names

FLT3LGFLFlt3 ligandFms-like tyrosine kinase 3 ligand

FLT3L acts as an agonist by binding to the FLT3 receptor, inducing receptor homodimerization and activating downstream signaling pathways such as PI3K/AKT, RAS/MAPK, and JAK/STAT to promote cell survival and differentiation (PubMed: 10648404). Therapeutic antibodies act as antagonists by sequestering the ligand and preventing receptor activation.