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- W3205608051 endingPage "5084" @default.
- W3205608051 startingPage "5084" @default.
- W3205608051 abstract "Lenalidomide as well as other immunomodulatory drugs (IMiDs) have achieved clinical efficacies in certain sub-types of hematologic malignancies, such as multiple myeloma, lower-risk myelodysplastic syndromes (MDS) with a single deletion of chromosome 5q (del(5q)) and others. Despite superior clinical response to lenalidomide in hematologic malignancies, relapse and resistance remains a problem in IMiD-based therapy. The last ten years have witnessed the discovery of novel molecular mechanism of IMiD-based anti-tumor therapy. IMiDs bind human cereblon (CRBN), the substrate receptor of the CRL4 E3 ubiquitin ligase complex. Binding of CRBN with IMiDs leads to degradation of the Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3) and casein kinase 1 alpha. We have found that lenalidomide-mediated degradation of IKZF1 leads to activation of the G protein-coupled receptor 68 (GPR68)/calcium/calpain pro-apoptotic pathway and inhibition of the regulator of calcineurin 1 (RCAN1)/calcineurin pro-survival pathway in MDS and acute myeloid leukemia (AML). Calcineurin inhibitor Cyclosporin-A potentiates the anti-leukemia activity of lenalidomide in MDS/AML with or without del(5q). These findings broaden the therapeutic potential of IMiDs. This review summarizes novel molecular mechanism of lenalidomide in myeloid malignancies, especially without del(5q), in the hope to highlight novel therapeutic targets." @default.
- W3205608051 created "2021-10-25" @default.
- W3205608051 creator A5068661721 @default.
- W3205608051 creator A5068757629 @default.
- W3205608051 creator A5076671510 @default.
- W3205608051 date "2021-10-11" @default.
- W3205608051 modified "2023-10-15" @default.
- W3205608051 title "Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q" @default.
- W3205608051 cites W1483147211 @default.
- W3205608051 cites W1527383154 @default.
- W3205608051 cites W1717123962 @default.
- W3205608051 cites W1868158647 @default.
- W3205608051 cites W1964370179 @default.
- W3205608051 cites W1969889854 @default.
- W3205608051 cites W1970209924 @default.
- W3205608051 cites W1970838453 @default.
- W3205608051 cites W1975213528 @default.
- W3205608051 cites W1979627226 @default.
- W3205608051 cites W1981403111 @default.
- W3205608051 cites W1982589355 @default.
- W3205608051 cites W1982910988 @default.
- W3205608051 cites W1984065010 @default.
- W3205608051 cites W1984739493 @default.
- W3205608051 cites W1987383967 @default.
- W3205608051 cites W1987435826 @default.
- W3205608051 cites W1988327939 @default.
- W3205608051 cites W1989366736 @default.
- W3205608051 cites W1989595541 @default.
- W3205608051 cites W1991753383 @default.
- W3205608051 cites W1992538067 @default.
- W3205608051 cites W1995505548 @default.
- W3205608051 cites W1997952190 @default.
- W3205608051 cites W1999088487 @default.
- W3205608051 cites W2011109198 @default.
- W3205608051 cites W2015345028 @default.
- W3205608051 cites W2016553429 @default.
- W3205608051 cites W2018289001 @default.
- W3205608051 cites W2019828567 @default.
- W3205608051 cites W2020828641 @default.
- W3205608051 cites W2021333892 @default.
- W3205608051 cites W2021954218 @default.
- W3205608051 cites W2025030626 @default.
- W3205608051 cites W2027500843 @default.
- W3205608051 cites W2027616201 @default.
- W3205608051 cites W2033556677 @default.
- W3205608051 cites W2034220305 @default.
- W3205608051 cites W2040541876 @default.
- W3205608051 cites W2041893888 @default.
- W3205608051 cites W2042916026 @default.
- W3205608051 cites W2046479005 @default.
- W3205608051 cites W2048365283 @default.
- W3205608051 cites W2049005444 @default.
- W3205608051 cites W2052041910 @default.
- W3205608051 cites W2053816835 @default.
- W3205608051 cites W2054512969 @default.
- W3205608051 cites W2055028613 @default.
- W3205608051 cites W2056923064 @default.
- W3205608051 cites W2057514629 @default.
- W3205608051 cites W2064679601 @default.
- W3205608051 cites W2066053804 @default.
- W3205608051 cites W2066475453 @default.
- W3205608051 cites W2066713758 @default.
- W3205608051 cites W2068412287 @default.
- W3205608051 cites W2071959000 @default.
- W3205608051 cites W2076201989 @default.
- W3205608051 cites W2077678481 @default.
- W3205608051 cites W2078761761 @default.
- W3205608051 cites W2081870738 @default.
- W3205608051 cites W2082573799 @default.
- W3205608051 cites W2084778320 @default.
- W3205608051 cites W2085925586 @default.
- W3205608051 cites W2086029676 @default.
- W3205608051 cites W2086068555 @default.
- W3205608051 cites W2086905870 @default.
- W3205608051 cites W2087226541 @default.
- W3205608051 cites W2091106275 @default.
- W3205608051 cites W2091253809 @default.
- W3205608051 cites W2094823633 @default.
- W3205608051 cites W2097671458 @default.
- W3205608051 cites W2099308699 @default.
- W3205608051 cites W2100695910 @default.
- W3205608051 cites W2101085456 @default.
- W3205608051 cites W2101603234 @default.
- W3205608051 cites W2106233921 @default.
- W3205608051 cites W2112478541 @default.
- W3205608051 cites W2114492363 @default.
- W3205608051 cites W2115859409 @default.
- W3205608051 cites W2116194748 @default.
- W3205608051 cites W2119601553 @default.
- W3205608051 cites W2121533623 @default.
- W3205608051 cites W2123090800 @default.
- W3205608051 cites W2128079392 @default.
- W3205608051 cites W2128338459 @default.
- W3205608051 cites W2129119273 @default.
- W3205608051 cites W2129539691 @default.
- W3205608051 cites W2132258376 @default.
- W3205608051 cites W2132725936 @default.
- W3205608051 cites W2133832061 @default.