{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:33:59Z","timestamp":1787754839101,"version":"build-2784847793"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.<\/jats:p>","DOI":"10.3389\/fphar.2024.1404092","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:55:58Z","timestamp":1720054558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia"],"prefix":"10.3389","volume":"15","author":[{"given":"Yan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyuan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1182\/blood-2016-09-736686","article-title":"Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab","volume":"129","author":"Abaza","year":"2017","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"120884","DOI":"10.1016\/j.lfs.2022.120884","article-title":"All-trans retinoic acid-mediated miR-30a up-regulation suppresses autophagy and sensitizes gastric cancer cells to cisplatin","volume":"307","author":"Abbasi","year":"2022","journal-title":"Life Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e12901","DOI":"10.1111\/jpi.12901","article-title":"Angiogenesis, coagulation, and fibrinolytic markers in acute promyelocytic leukemia (NB4): an evaluation of melatonin effects","volume":"75","author":"Amirzargar","year":"2023","journal-title":"J. pineal Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1038\/s41598-020-59101-4","article-title":"Role of vitamins A and D in BCR-ABL arf(-\/-) acute lymphoblastic leukemia","volume":"10","author":"Annu","year":"2020","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1111\/bjh.15673","article-title":"Class 1 HDAC and HDAC6 inhibition inversely regulates CD38 induction in myeloma cells via interferon-\u03b1 and ATRA","volume":"185","author":"Bat-Erdene","year":"2019","journal-title":"Br. J. Haematol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1158\/0008-5472.CAN-17-3415","article-title":"Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of antiangiogenic therapy","volume":"78","author":"Bauer","year":"2018","journal-title":"Cancer Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"949140","DOI":"10.3389\/fimmu.2022.949140","article-title":"Myeloid checkpoint blockade improves killing of T-acute lymphoblastic leukemia cells by an IgA2 variant of daratumumab","volume":"13","author":"Baumann","year":"2022","journal-title":"Front. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"848517","DOI":"10.3389\/fonc.2022.848517","article-title":"All-trans-retinoic acid combined with valproic acid can promote differentiation in myeloid leukemia cells by an autophagy dependent mechanism","volume":"12","author":"Benjamin","year":"2022","journal-title":"Front. Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s10238-022-00860-x","article-title":"The immunomodulatory role of all-trans retinoic acid in tumor microenvironment","volume":"23","author":"Bi","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"13345","DOI":"10.3390\/ijms222413345","article-title":"The role of ATRA, natural ligand of retinoic acid receptors, on EMT-related proteins in breast cancer: minireview","volume":"22","author":"Bobal","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1080\/17425247.2021.1919619","article-title":"All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks","volume":"18","author":"Borges","year":"2021","journal-title":"Expert Opin. drug Deliv."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e1315","DOI":"10.1038\/cddis.2014.261","article-title":"WIPI-dependent autophagy during neutrophil differentiation of NB4 acute promyelocytic leukemia cells","volume":"5","author":"Brigger","year":"2014","journal-title":"Cell death Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1861","DOI":"10.1038\/cddis.2015.236","article-title":"Activation of RAR\u03b1 induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity","volume":"6","author":"Brigger","year":"2015","journal-title":"Cell death Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.immuni.2015.02.003","article-title":"Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program","volume":"42","author":"Brown","year":"2015","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","first-page":"12089","DOI":"10.3390\/ijms241512089","article-title":"Deregulation of all-trans retinoic acid signaling and development in cancer","volume":"24","author":"Brown","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/cncr.22496","article-title":"A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment","volume":"109","author":"Burnett","year":"2007","journal-title":"Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S1470-2045(15)00193-X","article-title":"Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial","volume":"16","author":"Burnett","year":"2015","journal-title":"Lancet Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1095\/biolreprod.115.135145","article-title":"The role of retinoic acid (RA) in spermatogonial differentiation","volume":"94","author":"Busada","year":"2016","journal-title":"Biol. reproduction"},{"key":"B19","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1080\/10428194.2020.1839648","article-title":"Differentiation of acute myeloid leukemia (AML) cells with ATRA reduces (18)F-FDG uptake and increases sensitivity towards ABT-737-induced apoptosis","volume":"62","author":"Buschner","year":"2021","journal-title":"Leukemia lymphoma"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e01874","DOI":"10.1128\/AAC.01874-20","article-title":"Antifungal effect of all-trans retinoic acid against Aspergillus fumigatus in vitro and in a pulmonary aspergillosis in vivo model","volume":"65","author":"Campione","year":"2021","journal-title":"Antimicrob. agents Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1182\/blood.v88.3.1052.bloodjournal8831052","article-title":"In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: as2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha\/PML proteins","volume":"88","author":"Chen","year":"1996","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.3892\/mmr.2017.6858","article-title":"Lentivirus-mediated RIG-I knockdown relieves cell proliferation inhibition, cell cycle arrest and apoptosis in ATRA-induced NB4 cells via the AKT-FOXO3A signaling pathway in vitro","volume":"16","author":"Chen","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1165\/rcmb.2017-0382OC","article-title":"All-trans retinoic acid augments autophagy during intracellular bacterial infection","volume":"59","author":"Coleman","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3390\/biomedicines9030237","article-title":"Trifarotene: a current review and perspectives in dermatology","volume":"9","author":"Cosio","year":"2021","journal-title":"Biomedicines"},{"key":"B25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/nu9010068","article-title":"Retinoic acid and its role in modulating intestinal innate immunity","volume":"9","author":"Czarnewski","year":"2017","journal-title":"Nutrients"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1038\/s41418-023-01139-8","article-title":"Targeting HDAC3 to overcome the resistance to ATRA or arsenic in acute promyelocytic leukemia through ubiquitination and degradation of PML-RAR\u03b1","volume":"30","author":"Dai","year":"2023","journal-title":"Cell death Differ."},{"key":"B27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.thromres.2016.02.013","article-title":"Efficacy of immunomodulatory therapy with all-trans retinoid acid in adult patients with chronic immune thrombocytopenia","volume":"140","author":"Dai","year":"2016","journal-title":"Thrombosis Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1182\/bloodadvances.2021006805","article-title":"Targeting hypersialylation in multiple myeloma represents a novel approach to enhance NK cell-mediated tumor responses","volume":"6","author":"Daly","year":"2022","journal-title":"Blood Adv."},{"key":"B29","doi-asserted-by":"publisher","first-page":"686445","DOI":"10.3389\/fonc.2021.686445","article-title":"The combination of gefitinib with ATRA and ATO induces myeloid differentiation in acute promyelocytic leukemia resistant cells","volume":"11","author":"de Almeida","year":"2021","journal-title":"Front. Oncol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s41580-023-00585-z","article-title":"Autophagy and autophagy-related pathways in cancer","volume":"24","author":"Debnath","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2014.12.003","article-title":"Retinoic acid receptors: from molecular mechanisms to cancer therapy","volume":"41","author":"di Masi","year":"2015","journal-title":"Mol. aspects Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.fct.2017.10.053","article-title":"Dasatinib synergizes with ATRA to trigger granulocytic differentiation in ATRA resistant acute promyelocytic leukemia cell lines via Lyn inhibition-mediated activation of RAF-1\/MEK\/ERK","volume":"119","author":"Ding","year":"2018","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Industrial Biol. Res. Assoc."},{"key":"B33","doi-asserted-by":"publisher","first-page":"144889","DOI":"10.1016\/j.gene.2020.144889","article-title":"Targeting ferroptosis contributes to ATPR-induced AML differentiation via ROS-autophagy-lysosomal pathway","volume":"755","author":"Du","year":"2020","journal-title":"Gene"},{"key":"B34","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.intimp.2018.10.041","article-title":"A novel all-trans retinoic acid derivative inhibits proliferation and induces apoptosis of myelodysplastic syndromes cell line SKM-1 cells via up-regulating p53","volume":"65","author":"Du","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1182\/blood-2014-11-612416","article-title":"Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells","volume":"125","author":"El Hajj","year":"2015","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.it.2016.12.006","article-title":"Retinoic acid and immune homeostasis: a balancing act","volume":"38","author":"Erkelens","year":"2017","journal-title":"Trends Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1182\/blood.v94.4.1192","article-title":"A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia","volume":"94","author":"Fenaux","year":"1999","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e487","DOI":"10.1016\/S2352-3026(17)30170-9","article-title":"Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial","volume":"4","author":"Feng","year":"","journal-title":"Lancet Haematol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1111\/jth.13767","article-title":"High-dose dexamethasone or all-trans-retinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia","volume":"15","author":"Feng","year":"","journal-title":"J. thrombosis haemostasis JTH"},{"key":"B40","doi-asserted-by":"publisher","first-page":"5128","DOI":"10.1182\/bloodadvances.2021005220","article-title":"Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed\/refractory multiple myeloma","volume":"5","author":"Frerichs","year":"2021","journal-title":"Blood Adv."},{"key":"B41","doi-asserted-by":"publisher","first-page":"568","DOI":"10.3324\/haematol.2022.281339","article-title":"All-trans retinoic acid works synergistically with the \u03b3-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T cells","volume":"108","author":"Garc\u00eda-Guerrero","year":"2023","journal-title":"Haematologica"},{"key":"B42","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1186\/s13046-023-02869-w","article-title":"Anti-tumor activity of all-trans retinoic acid in gastric-cancer: gene-networks and molecular mechanisms","volume":"42","author":"Guarrera","year":"2023","journal-title":"J. Exp. Clin. cancer Res. CR"},{"key":"B43","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1208\/s12248-021-00565-1","article-title":"The effects of all-trans retinoic acid on immune cells and its formulation design for vaccines","volume":"23","author":"Hao","year":"2021","journal-title":"AAPS J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ejphar.2014.10.064","article-title":"Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells","volume":"747","author":"Heo","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.neubiorev.2020.02.013","article-title":"Retinoic acid and depressive disorders: evidence and possible neurobiological mechanisms","volume":"112","author":"Hu","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B46","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1182\/blood.v72.2.567.bloodjournal722567","article-title":"Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia","volume":"72","author":"Huang","year":"1988","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.2147\/DDDT.S189969","article-title":"Notopterol-induced apoptosis and differentiation in human acute myeloid leukemia HL-60 cells","volume":"13","author":"Huang","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1182\/blood-2010-01-261040","article-title":"Autophagy contributes to therapy-induced degradation of the PML\/RARA oncoprotein","volume":"116","author":"Isakson","year":"2010","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/s13287-022-03053-1","article-title":"All-trans retinoic acid modulates pigmentation, neuroretinal maturation, and corneal transparency in human multiocular organoids","volume":"13","author":"Isla-Magran\u00e9","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"B50","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/leu.2008.362","article-title":"Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes? A report on 59 cases","volume":"23","author":"Itzykson","year":"2009","journal-title":"Leukemia"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1482795","DOI":"10.1155\/2018\/1482795","article-title":"Low autophagy (ATG) gene expression is associated with an immature AML blast cell phenotype and can Be restored during AML differentiation therapy","volume":"2018","author":"Jin","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1038\/s41375-019-0581-y","article-title":"The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML","volume":"33","author":"Kahl","year":"2019","journal-title":"Leukemia"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4451","DOI":"10.1038\/s41598-021-83939-x","article-title":"All-trans-retinoic acid ameliorates atherosclerosis, promotes perivascular adipose tissue browning, and increases adiponectin production in Apo-E mice","volume":"11","author":"Kalisz","year":"2021","journal-title":"Sci. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1194\/jlr.R037028","article-title":"Enzymology of retinoic acid biosynthesis and degradation","volume":"54","author":"Kedishvili","year":"2013","journal-title":"J. lipid Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3349\/ymj.2020.61.9.762","article-title":"All-trans retinoic acid synergizes with enasidenib to induce differentiation of IDH2-mutant acute myeloid leukemia cells","volume":"61","author":"Kim","year":"2020","journal-title":"Yonsei Med. J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e108863","DOI":"10.15252\/embj.2021108863","article-title":"Autophagy in major human diseases","volume":"40","author":"Klionsky","year":"2021","journal-title":"EMBO J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00277-005-0026-8","article-title":"Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia","volume":"84","author":"Kuendgen","year":"2005","journal-title":"Ann. Hematol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1182\/blood-2003-12-4333","article-title":"Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid","volume":"104","author":"Kuendgen","year":"2004","journal-title":"Blood"},{"key":"B59","doi-asserted-by":"publisher","first-page":"Cd011960","DOI":"10.1002\/14651858.CD011960.pub2","article-title":"Effects of all-trans retinoic acid (ATRA) in addition to chemotherapy for adults with acute myeloid leukaemia (AML) (non-acute promyelocytic leukaemia (non-APL))","volume":"8","author":"K\u00fcley-Bagheri","year":"2018","journal-title":"Cochrane database Syst. Rev."},{"key":"B60","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1001\/jamaoncol.2021.5206","article-title":"Assessment of arsenic trioxide and all-trans retinoic acid for the treatment of pediatric acute promyelocytic leukemia: a report from the children\u2019s oncology group AAML1331 trial","volume":"8","author":"Kutny","year":"2022","journal-title":"JAMA Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1182\/bloodadvances.2019001278","article-title":"A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535)","volume":"4","author":"Lancet","year":"2020","journal-title":"Blood Adv."},{"key":"B62","doi-asserted-by":"publisher","first-page":"4881","DOI":"10.1200\/JCO.22.02836","article-title":"Homoharringtonine-based induction regimen improved the remission rate and survival rate in Chinese childhood AML: a report from the CCLG-AML 2015 protocol study","volume":"41","author":"Li","year":"","journal-title":"J. Clin. Oncol. official J. Am. Soc. Clin. Oncol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e0174555","DOI":"10.1371\/journal.pone.0174555","article-title":"All-trans retinoic acid suppresses the angiopoietin-Tie2 pathway and inhibits angiogenesis and metastasis in esophageal squamous cell carcinoma","volume":"12","author":"Li","year":"2017","journal-title":"PloS one"},{"key":"B64","doi-asserted-by":"publisher","first-page":"174199","DOI":"10.1016\/j.ejphar.2021.174199","article-title":"A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1","volume":"906","author":"Li","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"110413","DOI":"10.1016\/j.intimp.2023.110413","article-title":"All-trans-retinoic acid inhibits hepatocellular carcinoma progression by targeting myeloid-derived suppressor cells and inhibiting angiogenesis","volume":"121","author":"Li","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.3892\/mmr.2014.2543","article-title":"Effects of all-trans retinoic acid on VEGF and HIF-1\u03b1 expression in glioma cells under normoxia and hypoxia and its anti-angiogenic effect in an intracerebral glioma model","volume":"10","author":"Liang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"113451","DOI":"10.1016\/j.ejmech.2021.113451","article-title":"Overview of all-trans-retinoic acid (ATRA) and its analogues: structures, activities, and mechanisms in acute promyelocytic leukaemia","volume":"220","author":"Liang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B68","doi-asserted-by":"publisher","first-page":"4221","DOI":"10.3892\/mmr.2016.5086","article-title":"Effect of ATRA on the expression of HOXA5 gene in K562 cells and its relationship with cell cycle and apoptosis","volume":"13","author":"Liu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B69","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic acid and arsenic trioxide for acute promyelocytic leukemia","volume":"369","author":"Lo-Coco","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"3361","DOI":"10.1080\/10428194.2021.1961231","article-title":"Trametinib enhances ATRA-induced differentiation in AML cells","volume":"62","author":"Lu","year":"2021","journal-title":"Leukemia lymphoma"},{"key":"B71","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1186\/s12885-022-09828-2","article-title":"Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3","volume":"22","author":"Lu","year":"2022","journal-title":"BMC cancer"},{"key":"B72","doi-asserted-by":"publisher","first-page":"174822","DOI":"10.1016\/j.ejphar.2022.174822","article-title":"ATRA promotes PD-L1 expression to control gastric cancer immune surveillance","volume":"920","author":"Ma","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e17810","DOI":"10.15252\/emmm.202317810","article-title":"The transcription factor HIF2\u03b1 partakes in the differentiation block of acute myeloid leukemia","volume":"15","author":"Magliulo","year":"2023","journal-title":"EMBO Mol. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3455","DOI":"10.1182\/blood-2014-11-611459","article-title":"Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells","volume":"125","author":"Martelli","year":"2015","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41408-022-00715-4","article-title":"The antileukemic activity of decitabine upon PML\/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation","volume":"12","author":"Meier","year":"2022","journal-title":"Blood cancer J."},{"key":"B76","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.3390\/ijms20143559","article-title":"Autophagy: new insights into mechanisms of action and resistance of treatment in acute promyelocytic leukemia","volume":"20","author":"Moosavi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1182\/blood.2020006200","article-title":"CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity","volume":"136","author":"Naeimi","year":"2020","journal-title":"Blood"},{"key":"B78","first-page":"2244","article-title":"Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML\/RARalpha fusion protein","volume":"92","author":"Nervi","year":"1998","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.1080\/10408398.2018.1509201","article-title":"The success and the challenge of all-trans retinoic acid in the treatment of cancer","volume":"59","author":"Ni","year":"2019","journal-title":"Crit. Rev. food Sci. Nutr."},{"key":"B80","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.tice.2014.11.004","article-title":"All trans retinoic acid modulates peripheral nerve fibroblasts viability and apoptosis","volume":"47","author":"Niapour","year":"2015","journal-title":"Tissue & Cell"},{"key":"B81","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1038\/leu.2015.123","article-title":"Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab","volume":"29","author":"Nijhof","year":"2015","journal-title":"Leukemia"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e006325","DOI":"10.1136\/jitc-2022-006325","article-title":"All-trans retinoic acid improves NSD2-mediated RAR\u03b1 phase separation and efficacy of anti-CD38 CAR T-cell therapy in multiple myeloma","volume":"11","author":"Peng","year":"2023","journal-title":"J. Immunother. cancer"},{"key":"B83","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/cncr.21132","article-title":"Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid","volume":"104","author":"Pilatrino","year":"2005","journal-title":"Cancer"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e12315","DOI":"10.1111\/cpr.12315","article-title":"All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo","volume":"50","author":"Pourjafar","year":"2017","journal-title":"Cell Prolif."},{"key":"B85","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1159\/000437326","article-title":"The effects of all-trans retinoic acid on the induction of oral tolerance in a murine model of bronchial asthma","volume":"167","author":"Sakamoto","year":"2015","journal-title":"Int. archives allergy Immunol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"104545","DOI":"10.1016\/j.phrs.2019.104545","article-title":"CDK2 suppression synergizes with all-trans-retinoic acid to overcome the myeloid differentiation blockade of AML cells","volume":"151","author":"Shao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"e2308617","DOI":"10.1002\/advs.202308617","article-title":"CD38-Specific gallium-68 labeled peptide radiotracer enables pharmacodynamic monitoring in multiple myeloma with PET","volume":"11","author":"Sharma","year":"2024","journal-title":"Adv. Sci. Weinheim, Baden-Wurttemberg, Ger."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2163784","DOI":"10.1080\/2162402X.2022.2163784","article-title":"Daratumumab induces cell-mediated cytotoxicity of primary effusion lymphoma and is active against refractory disease","volume":"12","author":"Shrestha","year":"2023","journal-title":"Oncoimmunology"},{"key":"B89","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1182\/blood-2007-03-078576","article-title":"Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome","volume":"110","author":"Soriano","year":"2007","journal-title":"Blood"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1182\/blood.v99.5.1578","article-title":"Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes","volume":"99","author":"Stasi","year":"2002","journal-title":"Blood"},{"key":"B91","first-page":"6425","article-title":"Novel nanoscale delivery particles encapsulated with anticancer drugs, all-trans retinoic acid or curcumin, enhance apoptosis in lymphoma cells predominantly expressing CD20 antigen","volume":"35","author":"Stauffer","year":"2015","journal-title":"Anticancer Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.3390\/cells9122660","article-title":"Retinoic acid and its derivatives in skin","volume":"9","author":"Szyma\u0144ski","year":"2020","journal-title":"Cells"},{"key":"B93","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1111\/bjh.16871","article-title":"All-trans-retinoic acid shifts Th1 towards Th2 cell differentiation by targeting NFAT1 signalling to ameliorate immune-mediated aplastic anaemia","volume":"191","author":"Tang","year":"2020","journal-title":"Br. J. Haematol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/j.molmed.2021.06.013","article-title":"Targeting low-risk myelodysplastic syndrome with novel therapeutic strategies","volume":"27","author":"Trivedi","year":"2021","journal-title":"Trends Mol. Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41408-022-00753-y","article-title":"An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial)","volume":"12","author":"Wang","year":"","journal-title":"Blood cancer J."},{"key":"B96","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.3390\/pharmaceutics14112329","article-title":"The translational landscape revealed the sequential treatment containing ATRA plus PI3K\/AKT inhibitors as an efficient strategy for AML therapy","volume":"14","author":"Wang","year":"","journal-title":"Pharmaceutics"},{"key":"B97","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s41416-022-02074-0","article-title":"All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RAR\u03b1-Nrf2 complex","volume":"128","author":"Wang","year":"2023","journal-title":"Br. J. cancer"},{"key":"B98","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1182\/blood.2020009856","article-title":"RAR\u03b3 activation sensitizes human myeloma cells to carfilzomib treatment through the OAS-RNase L innate immune pathway","volume":"139","author":"Wang","year":"","journal-title":"Blood"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1158\/1078-0432.CCR-15-0663","article-title":"Sorafenib inhibition of mcl-1 accelerates ATRA-induced apoptosis in differentiation-responsive AML cells","volume":"22","author":"Wang","year":"2016","journal-title":"Clin. cancer Res. official J. Am. Assoc. Cancer Res."},{"key":"B100","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13046-022-02421-2","article-title":"Expanding anti-CD38 immunotherapy for lymphoid malignancies","volume":"41","author":"Wang","year":"","journal-title":"J. Exp. Clin. cancer Res. CR"},{"key":"B101","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.omtn.2020.04.013","article-title":"miRNA-98-5p targeting IGF2BP1 induces mesenchymal stem cell apoptosis by modulating PI3K\/Akt and p53 in immune thrombocytopenia","volume":"20","author":"Wang","year":"2020","journal-title":"Mol. Ther. Nucleic acids"},{"key":"B102","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/s1470-2045(00)00017-6","article-title":"Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia","volume":"1","author":"Wang","year":"2000","journal-title":"Lancet Oncol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41375-020-0892-z","article-title":"A proof of concept phase I\/II pilot trial of LSD1 inhibition by tranylcypromine combined with ATRA in refractory\/relapsed AML patients not eligible for intensive therapy","volume":"35","author":"Wass","year":"2021","journal-title":"Leukemia"},{"key":"B104","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.leukres.2016.03.008","article-title":"RAF-1\/MEK\/ERK pathway regulates ATRA-induced differentiation in acute promyelocytic leukemia cells through C\/EBP\u03b2, C\/EBP\u03b5 and PU.1","volume":"45","author":"Weng","year":"2016","journal-title":"Leukemia Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.18240\/ijo.2020.09.01","article-title":"All-trans retinoic acid increases ARPE-19 cell apoptosis via activation of reactive oxygen species and endoplasmic reticulum stress pathways","volume":"13","author":"Wu","year":"2020","journal-title":"Int. J. Ophthalmol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s00277-016-2681-3","article-title":"Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy","volume":"95","author":"Wu","year":"2016","journal-title":"Ann. Hematol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1182\/blood.2021013393","article-title":"All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP","volume":"139","author":"Wu","year":"2022","journal-title":"Blood"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1089\/scd.2017.0078","article-title":"Impaired function of bone marrow mesenchymal stem cells from immune thrombocytopenia patients in inducing regulatory dendritic cell differentiation through the notch-1\/jagged-1 signaling pathway","volume":"26","author":"Xu","year":"2017","journal-title":"Stem cells Dev."},{"key":"B109","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1007\/s00277-023-05263-w","article-title":"All-trans retinoic acid added to treatment of primary immune thrombocytopenia: a systematic review and meta-analysis","volume":"102","author":"Yang","year":"2023","journal-title":"Ann. Hematol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41408-021-00514-3","article-title":"Acute promyelocytic leukemia current treatment algorithms","volume":"11","author":"Yilmaz","year":"2021","journal-title":"Blood cancer J."},{"key":"B111","doi-asserted-by":"publisher","first-page":"e116","DOI":"10.1038\/cti.2016.73","article-title":"All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia","volume":"5","author":"Yoshida","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1056\/NEJMra1413485","article-title":"Aplastic anemia","volume":"379","author":"Young","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B113","doi-asserted-by":"publisher","first-page":"110304","DOI":"10.1016\/j.cellsig.2022.110304","article-title":"ATRA-mediated-crosstalk between stellate cells and Kupffer cells inhibits autophagy and promotes NLRP3 activation in acute liver injury","volume":"93","author":"Yu","year":"2022","journal-title":"Cell. Signal."},{"key":"B114","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.leukres.2005.11.017","article-title":"Successful treatment of primary refractory anemia with a combination regimen of all-trans retinoic acid, calcitriol, and androgen","volume":"30","author":"Zhang","year":"2006","journal-title":"Leukemia Res."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.3109\/10428190109097751","article-title":"Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies","volume":"42","author":"Zhao","year":"2001","journal-title":"Leukemia lymphoma"},{"key":"B116","doi-asserted-by":"publisher","first-page":"829391","DOI":"10.3389\/fimmu.2022.829391","article-title":"Sustained drug release from liposomes for the remodeling of systemic immune homeostasis and the tumor microenvironment","volume":"13","author":"Zheng","year":"2022","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1404092\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:56:02Z","timestamp":1720054562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1404092\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,4]]},"references-count":116,"alternative-id":["10.3389\/fphar.2024.1404092"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1404092","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,4]]},"article-number":"1404092"}}