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Merck

Molecular targeting of inosine-5'-monophosphate dehydrogenase by FF-10501 promotes erythropoiesis via ROS/MAPK pathway.

Leukemia & lymphoma (2017-07-22)
Michiko Ichii, Kenji Oritani, Motohiko Murase, Kensuke Komatsu, Mao Yamazaki, Rie Kyoden, Nobuko Kito, Yusuke Nozaki, Motoki Saito, Hiroyuki Iwamura, Yuzuru Kanakura
RESUMEN

One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5'-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner. Interestingly, we found that metabolic conversion of IMP to hypoxanthine leads to elevation of reactive oxygen species (ROS). The differentiative effects of FF-10501 were abolished by the ROS scavenger dimethylthiourea or the p38 MAPK inhibitor SB203580. Furthermore, FF-10501 promoted erythropoiesis from CD34

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Ácido retinoico, ≥98% (HPLC), powder
Sigma-Aldrich
Calcein, Used for the fluorometric determination of calcium and EDTA titration of calcium in the presence of magnesium.
Sigma-Aldrich
7-Aminoactinomycin D, ~97% (HPLC), powder