Leukemia inhibitory factor receptor α-chain: a potential method for acute promyeloid leukemia therapy

Leukemia inhibitory factor (LIF) affects multiple types of leukemia cells in vitro through its functional receptor LIFR, which comprises a complex of the LIFR α-chain (LIFRα) and gp130. Researchers have recently observed that the C-terminus of the LIFRα cytoplasmic domain contains as many conserved YXXQ motifs as gp130 (C-terminal triple YXXQ motifs, LIFRα-CT3), whose free structure has been shown to be capable of activating STAT3 phosphorylation in the cytoplasm and consequently activating STAT3-related downstream molecules in the nucleus. This process can induce pathological acute myeloid leukemia (AML) or acute promyeloid leukemia (APL) cells to differentiate into mature granulocytes, simulating the LIF-related differential cascade. This process reduces or inhibits the side effects caused by toxic all-trans retinoid acid (ATRA), which has long been used as a fundamental medication for treating AML/APL in clinical practice despite its related high relapse rate. Therefore, we believe that it is possible to maximize the beneficial effects of LIF by enriching LIFRα-CT3 in AML/APL cell cytoplasm. The aims of this work were to enrich LIFRα-specific motifs in leukemia cells using molecular biological methods and evaluate the use of membrane-permeable polypeptides as a novel possible AML/APL therapy in combination with or independent of ATRA-based chemotherapy.