dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Lozano, Maria L. |
dc.contributor.author | Segú-Vergés, Cristina |
dc.contributor.author | Coma, Mireia |
dc.contributor.author | González-Porras, José R. |
dc.contributor.author | Gutiérrez, Laura |
dc.contributor.author | Valcarcel Ferreiras, David |
dc.contributor.author | Álvarez Román, María Teresa |
dc.date.accessioned | 2022-02-22T07:38:17Z |
dc.date.available | 2022-02-22T07:38:17Z |
dc.date.issued | 2021-07 |
dc.identifier.citation | Lozano ML, Segú-Vergés C, Coma M, Álvarez-Roman MT, González-Porras JR, Gutiérrez L, et al. Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach. Int J Mol Sci. 2021 Jul;22(13):6907. |
dc.identifier.issn | 1422-0067 |
dc.identifier.uri | https://hdl.handle.net/11351/7053 |
dc.description | Artificial intelligence; Eltrombopag; Primary immune thrombocytopenia |
dc.description.abstract | Eltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP. |
dc.language.iso | eng |
dc.publisher | MDPI |
dc.relation.ispartofseries | International Journal of Molecular Sciences;22(13) |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Trombocitopènia - Tractament |
dc.subject | Trombopoetina - Receptors |
dc.subject.mesh | Purpura, Thrombocytopenic, Idiopathic |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Receptors, Thrombopoietin |
dc.subject.mesh | /antagonists & inhibitors |
dc.title | Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.3390/ijms22136907 |
dc.subject.decs | púrpura trombocitopénica idiopática |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | receptores de trombopoyetina |
dc.subject.decs | /antagonistas & inhibidores |
dc.relation.publishversion | https://doi.org/10.3390/ijms22136907 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Lozano ML] Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CB15/00055-CIBERER, 30007 Murcia, Spain. [Segú-Vergés C, Coma M] Anaxomics Biotech S.L., 08007 Barcelona, Spain. [Álvarez-Roman MT] Unidad de Trombosis y Hemostasia, Servicio de Hematología, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain. [González-Porras JR] Unidad de Hemostasia y Trombosis, Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain. [Gutiérrez L] Grupo de Investigación en Plaquetas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Departamento de Medicina, Universidad de Oviedo, 33071 Oviedo, Spain. [Valcárcel D] Vall d’Hebron Insitute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain |
dc.identifier.pmid | 34199099 |
dc.identifier.wos | 000670936400001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |