{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:56Z","timestamp":1787028476521,"version":"build-2736575974"},"reference-count":188,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of \u22651.0 \u00d7 109 blasts\/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients\u2019 outcomes. A mitogen-activated protein kinase\/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids\u2019 mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.<\/jats:p>","DOI":"10.3390\/ijms23073795","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:22:14Z","timestamp":1648675334000},"page":"3795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia\u2014The State-of-the-Art Knowledge and Future Prospects"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-8831","authenticated-orcid":false,"given":"Kamil","family":"Ko\u015bmider","sequence":"first","affiliation":[{"name":"Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Karska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Kozakiewicz","sequence":"additional","affiliation":[{"name":"Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnostics, Medical University of Lublin, G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-156X","authenticated-orcid":false,"given":"Joanna","family":"Zawitkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6429","DOI":"10.1038\/sj.onc.1207717","article-title":"Epidemiology and Genetics of Childhood Cancer","volume":"23","author":"Stiller","year":"2004","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5493\/wjem.v3.i2.21","article-title":"Steroid Resistance in Leukemia","volume":"3","author":"Shah","year":"2013","journal-title":"World J. 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