2026-06-27T23:51:52Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/954862025-09-18T17:47:36Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author López Millán, Belén author Anguita Mandly, Eduardo Luis author Menéndez, Pablo 2024-01-25T13:57:23Z 2024-01-25T13:57:23Z 2018 Lopez-Millan B, Diaz de la Guardia R, Roca-Ho H, Anguita E, Islam ABMMK, Romero-Moya D, Prieto C, Gutierrez-Agüera F, Bejarano-Garcia JA, Perez-Simon JA, Costales P, Rovira M, Marín P, Menendez S, Iglesias M, Fuster JL, Urbano-Ispizua A, Anjos-Afonso F, Bueno C, Menendez P. IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML. Oncoimmunology. 2018 Jul 26;7(9):e1477460. 2162-402X 10.1080/2162402x.2018.1477460 https://hdl.handle.net/20.500.14352/95486 https://doi.org/10.1080/2162402X.2018.1477460 Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients remain refractory or relapse upon standard chemotherapy based on nucleoside analogs plus anthracyclines. The crosstalk between AML cells and the BM stroma is a major mechanism underlying therapy resistance in AML. Lenalidomide and pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess pleio-tropic anti-leukemic properties including potent immune-modulating effects and are commonly used in hematological malignances associated with intrinsic dysfunctional BM such as myelodysplastic syndromes and multiple myeloma. Whether IMiDs may improve the efficacy of current standard treatment in AML remains understudied. Here, we have exploited in vitro and in vivo preclinical AML models to analyze whether IMiDs potentiate the efficacy of AraC/Idarubicin-based standard AML chemotherapy by interfering with the BM stroma-mediated chemoresistance. We report that IMiDs do not exert cytotoxic effects on either non-del5q/5q- AML cells nor BM-MSCs, but they enhance the immunomodulatory properties of BM-MSCs. When combined with AraC/Idarubicin, IMiDs fail to circumvent BM stroma-mediated resistance of non-del5q/5q- AML cells in vitro and in vivo but induce robust extramedullary mobilization of AML cells. When administered as a single agent, lenalidomide specifically mobilizes non-del5q/5q- AML cells, but not healthy CD34+cells, to peripheral blood (PB) through specific down-regulation of CXCR4 in AML blasts. Global gene expression profiling supports a migratory/mobilization gene signature in lenalidomide-treated non-del5q/5q- AML blasts but not in CD34+cells. Collectively, IMiDs mobilize non-del5q/5q- AML blasts to PB through CXCR4 downregulation, but fail to potentiate AraC/Idarubicin activity in preclinical models of non-del5q/5q- AML. eng Attribution-NonCommercial-NoDerivatives 4.0 International IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML journal article 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URL https://docta.ucm.es/bitstreams/52750aeb-2081-48ea-8f4b-f0c66a81c5bf/download File MD5 57fca8fe9a44842600a74010dafd35b5 3497734 application/pdf IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC Idarubicin activity in pr.pdf URL https://docta.ucm.es/bitstreams/0ac0908b-4a0a-44fa-855d-6774ae738b4b/download File MD5 6ecd67158f441fac1e5318d5646ef5de 61620 text/plain IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC Idarubicin activity in pr.pdf.txt