Jawad N, McHugh K. The clinical and radiologic features of paediatric rhabdomyosarcoma. Pediatr Radiol. 2019;49:1516–23.

Article  PubMed  Google Scholar 

Williamson D, Missiaglia E, Reyniès AD, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Laé M, Fréneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol. 2010;28:2151–8.

Article  PubMed  Google Scholar 

Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F, Concordet J-P, Thway K, Oberlin O, Pritchard-Jones K, Delattre O, Delorenzi M, Shipley J. PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. J Clin Oncol. 2012;30:1670–7.

Article  PubMed  Google Scholar 

Skapek SX, Anderson J, Barr FG, Bridge JA, Gastier-Foster JM, Parham DM, Rudzinski ER, Triche T, Hawkins DS. PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: a children’s oncology group report. Pediatr Blood Cancer. 2013;60:1411–7.

Article  PubMed  PubMed Central  Google Scholar 

Breneman JC, Lyden E, Pappo AS, Link MP, Anderson JR, Parham DM, Qualman SJ, Wharam MD, Donaldson SS, Maurer HM, Meyer WH, Baker KS, Paidas CN, Crist WM. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma—a report from the intergroup rhabdomyosarcoma study IV. J Clin Oncol. 2003;21:78–84.

Article  PubMed  Google Scholar 

Egas-Bejar D, Huh WW. Rhabdomyosarcoma in adolescent and young adult patients: current perspectives. Adolesc Health Med Therap. 2014;5:115–25.

Google Scholar 

Ciarapica R, Carcarino E, Adesso L, De Salvo M, Bracaglia G, Leoncini PP, Dall’Agnese A, Verginelli F, Milano GM, Boldrini R, Inserra A, Stifani S, Screpanti I, Marquez VE, Valente S, Mai A, Puri PL, Locatelli F, Palacios D, Rota R. Pharmacological inhibition of EZH2 as a promising differentiation therapy in embryonal RMS. BMC Cancer. 2014;14:139.

Article  PubMed  PubMed Central  Google Scholar 

Ramaglia M, D’Angelo V, Iannotta A, Di Pinto D, Pota E, Affinita MC, Donofrio V, Errico ME, Lombardi A, Indolfi C, Casale F, Caraglia M. High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas. Cancer Cell Int. 2016;16:59.

Article  PubMed  PubMed Central  Google Scholar 

Chen YH, Hung MC, Li LY. EZH2: a pivotal regulator in controlling cell differentiation. Am J Transl Res. 2012;4:364–75.

CAS  PubMed  PubMed Central  Google Scholar 

Caretti G, Di Padova M, Micales B, Lyons GE, Sartorelli V. The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev. 2004;18:2627–38.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marchesi I, Fiorentino FP, Rizzolio F, Giordano A, Bagella L. The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation. Cell Cycle. 2012;11:3828–36.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marchesi I, Sanna L, Fais M, Fiorentino FP, Giordano A, Bagella L. 12-O-tetradecanoylphorbol-13-acetate and EZH2 inhibition: a novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells. J Cell Physiol. 2018;233:2360–5.

Article  CAS  PubMed  Google Scholar 

Ciarapica R, De Salvo M, Carcarino E, Bracaglia G, Adesso L, Leoncini PP, Dall’Agnese A, Walters ZS, Verginelli F, De Sio L, Boldrini R, Inserra A, Bisogno G, Rosolen A, Alaggio R, Ferrari A, Collini P, Locatelli M, Stifani S, Screpanti I, Rutella S, Yu Q, Marquez VE, Shipley J, Valente S, Mai A, Miele L, Puri PL, Locatelli F, Palacios D, Rota R. The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx). Oncogene. 2014;33:4173–84.

Article  CAS  PubMed  Google Scholar 

Schmidt A, Behrendt L, Eybe J, Warmann SW, Schleicher S, Fuchs J, Schmid E. The effect of direct and indirect EZH2 inhibition in rhabdomyosarcoma cell lines. Cancers. 2022;14:41.

Article  CAS  Google Scholar 

Walters ZS, Villarejo-Balcells B, Olmos D, Buist TW, Missiaglia E, Allen R, Al-Lazikani B, Garrett MD, Blagg J, Shipley J. JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells. Oncogene. 2014;33:1148–57.

Article  CAS  PubMed  Google Scholar 

Romanelli A, Stazi G, Fioravanti R, Zwergel C, Di Bello E, Pomella S, Perrone C, Battistelli C, Strippoli R, Tripodi M, Del Bufalo D, Rota R, Trisciuoglio D, Mai A, Valente S. Design of first-in-class dual EZH2/HDAC inhibitor: biochemical activity and biological evaluation in cancer cells. ACS Med Chem Lett. 2020;11:977–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Siddikuzzaman C, Guruvayoorappan VM. Berlin grace, all trans retinoic acid and cancer. Immunopharmacol Immunotoxicol. 2011;33:241–9.

Article  CAS  PubMed  Google Scholar 

Hunsu VO, Facey COB, Fields JZ, Boman BM. Retinoids as chemo-preventive and molecular-targeted anti-cancer therapies. Int J Mol Sci. 2021;22:7731.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rytlewski J, Milhem MM, Monga V. Turning “cold” tumors “hot”: immunotherapies in sarcoma. Ann Transl Med. 2021;9:1039.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.

Article  CAS  PubMed  Google Scholar 

Peinemann F, van Dalen EC, Enk H, Berthold F. Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2017;8:Cd010685.

PubMed  Google Scholar 

Al-Tahan A, Sarkis O, Harajly M, Baghdadi OK, Zibara K, Boulos F, Dighe D, Kregel S, Bazarbachi A, El-Sabban M, Skapek SX, Saab R. Retinoic acid fails to induce cell cycle arrest with myogenic differentiation in rhabdomyosarcoma. Pediatr Blood Cancer. 2012;58:877–84.

Article  PubMed  Google Scholar 

Bayeva N, Coll E, Piskareva O. Differentiating neuroblastoma: a systematic review of the retinoic acid its derivatives, and synergistic interactions. J Pers Med. 2021;11:211.

Article  PubMed  PubMed Central  Google Scholar 

Connolly RM, Nguyen NK, Sukumar S. Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res. 2013;19:1651–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crouch GD, Helman LJ. All-trans-retinoic acid inhibits the growth of human rhabdomyosarcoma cell lines. Cancer Res. 1991;51:4882–7.

CAS  PubMed  Google Scholar 

Barlow JW, Wiley JC, Mous M, Narendran A, Gee MFW, Goldberg M, Sexsmith E, Malkin D. Differentiation of rhabdomyosarcoma cell lines using retinoic acid. Pediatr Blood Cancer. 2006;47:773–84.

Article  PubMed  Google Scholar 

Swords RT, Perez A, Rodriguez A, Watts JM, Schenk T, Vargas F, Elias R, Zelent A. In acute myeloid leukemia (AML), targeting the histone methyltransferase EZH2 promotes differentiation, impairs clonogenic survival and augments the anti-leukemic effects of the retinoid, all-trans-retinoic acid (ATRA). Blood. 2015;126:3786.

Article  Google Scholar 

Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, Giordano A. Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle. 2009;8:172–5.

Article  CAS  PubMed  Google Scholar 

Sun W, Chatterjee B, Wang Y, Stevenson HS, Edelman DC, Meltzer PS, Barr FG. Distinct methylation profiles characterize fusion-positive and fusion-negative rhabdomyosarcoma. Mod Pathol. 2015;28:1214–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

R2: Genomics Analysis and Visualization Platform.

Kawano S, Grassian AR, Tsuda M, Knutson SK, Warholic NM, Kuznetsov G, Xu S, Xiao Y, Pollock RM, Smith JS, Kuntz KK, Ribich S, Minoshima Y, Matsui J, Copeland RA, Tanaka S, Keilhack H. Preclinical evidence of anti-tumor activity induced by EZH2 inhibition in human models of synovial sarcoma. PLoS ONE. 2016;11:e0158888.

Article  PubMed  PubMed Central  Google Scholar 

Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8:1324–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA. Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol. 2010;148:3–15.

Article  CAS  PubMed  Google Scholar 

Estler M, Boskovic G, Denvir J, Miles S, Primerano DA, Niles RM. Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma. BMC Genom. 2008;9:478.

Article  Google Scholar 

Zhang J, Gao Y, Yu M, Wu H, Ai Z, Wu Y, Liu H, Du J, Guo Z, Zhang Y. Retinoic acid induces embryonic stem cell differentiation by altering both encoding RNA and microRNA expression. PLoS ONE. 2015;10:e0132566.

Article  PubMed  PubMed Central  Google Scholar