{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:35:34Z","timestamp":1793212534649,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Early relapse and a poor prognosis are standard features of T-acute lymphoblastic leukemia (T-ALL), a hematological malignancy that presents significant treatment challenges. Glucocorticoids (GCs) are the first line of treatment for T-ALL; nevertheless, GC resistance may develop in patients with newly diagnosed and recurrent T-ALL due to abnormalities in apoptotic pathways. Here, we investigated the impact of the targeted medication, selumetinib, on the expression of proteins that regulate apoptosis in malignant T-ALL cells. We examined the Bcl-2, Bax, P53, Beclin1, and NFE2L2 expression levels as proteins directly or indirectly regulating the apoptosis pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Jurkat cells were treated with different concentrations of selumetinib. Cell viability and IC50 values were measured using the Alamar Blue assay. Gene expression profiles of Bcl-2, Bax, P53, Beclin1, and NFE2L2 were assessed using real-time PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The results revealed that selumetinib significantly increased P53, Bax gene expression (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), and Bax\/Bcl-2 ratio in a time- and dose-dependent manner. A significant decrease was also observed in Beclin1 and NFE2L2 expression (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The study presented here showed that selumetinib at higher doses induced Bax and P53 expression levels and did not affect Bcl-2 in Jurkat cells. This suggests that selumetinib may significantly induce apoptosis in apoptosis-defective T-ALL cells. Moreover, at lower doses, by reducing the expression of Beclin1 and NFE2L2, selumetinib may inhibit the autophagy-dependent survival pathway and induce apoptosis through increasing ROS in patients with newly diagnosed or relapsed ALL, respectively.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/abr.abr_422_24","type":"journal-article","created":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:00:21Z","timestamp":1793210421000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Selumetinib Inhibits T-Acute Lymphoblastic Leukemia Cell Proliferation by Inducing Apoptosis, Inhibiting Autophagy, and Modulating Reactive Oxygen Species Pathway"],"prefix":"10.4103","volume":"15","author":[{"given":"Faeze","family":"Bagherifar","sequence":"first","affiliation":[{"name":"Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pejman","family":"Hamedi-Asl","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepide","family":"Shakeri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Ayatollahi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad 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