Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag
In the last years, the use of thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has improved the management of immune thrombocytopenia (ITP). Moreover, eltrombopag is also active in patients with aplastic anemia and myelodysplastic syndrome. However, their mechanisms of action...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-11-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2019.1702156 |
| _version_ | 1797684184786927616 |
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| author | Jesús María Hernández-Sánchez José María Bastida Diego Alonso-López Rocío Benito José Ramón González-Porras Javier De Las Rivas Jesús María Hernández Rivas Ana Eugenia Rodríguez-Vicente |
| author_facet | Jesús María Hernández-Sánchez José María Bastida Diego Alonso-López Rocío Benito José Ramón González-Porras Javier De Las Rivas Jesús María Hernández Rivas Ana Eugenia Rodríguez-Vicente |
| author_sort | Jesús María Hernández-Sánchez |
| collection | DOAJ |
| description | In the last years, the use of thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has improved the management of immune thrombocytopenia (ITP). Moreover, eltrombopag is also active in patients with aplastic anemia and myelodysplastic syndrome. However, their mechanisms of action and signaling pathways still remain controversial. In order to gain insight into the mechanisms underlying eltrombopag therapy, a gene expression profile (GEP) analysis in patients treated with this drug was carried out. Fourteen patients with chronic ITP were studied by means of microarrays before and during eltrombopag treatment. Median age was 78 years (range, 35–87 years); median baseline platelet count was 14 × 109/L (range, 2–68 × 109/L). Ten patients responded to the therapy, two cases relapsed after an initial response and the remaining two were refractory to the therapy. Eltrombopag induced relevant changes in the hematopoiesis, platelet activation and degranulation, as well as in megakaryocyte differentiation, with overexpression of some transcription factors and the genes PPBP, ITGB3, ITGA2B, F13A1, F13A1, MYL9 and ITGA2B. In addition, GP1BA, PF4, ITGA2B, MYL9, HIST1H4H and HIST1H2BH, genes regulated by RUNX1 were also significantly enriched after eltrombopag therapy. Furthermore, in non-responder patients, an overexpression of Bcl-X gene and genes involved in erythropoiesis, such as SLC4A1 and SLC25A39, was also observed. To conclude, overexpression in genes involved in megakaryopoiesis, platelet adhesion, degranulation and aggregation was observed in patients treated with eltrombopag. Moreover, an important role regarding heme metabolism was also present in non-responder patients. |
| first_indexed | 2024-03-12T00:25:54Z |
| format | Article |
| id | doaj.art-1d058db6f211498e816e3ec8ee6e8695 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:25:54Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-1d058db6f211498e816e3ec8ee6e86952023-09-15T10:32:02ZengTaylor & Francis GroupPlatelets0953-71041369-16352020-11-01318993100010.1080/09537104.2019.17021561702156Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopagJesús María Hernández-Sánchez0José María Bastida1Diego Alonso-López2Rocío Benito3José Ramón González-Porras4Javier De Las Rivas5Jesús María Hernández Rivas6Ana Eugenia Rodríguez-Vicente7Hospital Universitario SalamancaHospital Universitario SalamancaCancer Research Center (CSIC-USAL)Hospital Universitario SalamancaHospital Universitario SalamancaCancer Research Center (CSIC-USAL)Hospital Universitario SalamancaHospital Universitario SalamancaIn the last years, the use of thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has improved the management of immune thrombocytopenia (ITP). Moreover, eltrombopag is also active in patients with aplastic anemia and myelodysplastic syndrome. However, their mechanisms of action and signaling pathways still remain controversial. In order to gain insight into the mechanisms underlying eltrombopag therapy, a gene expression profile (GEP) analysis in patients treated with this drug was carried out. Fourteen patients with chronic ITP were studied by means of microarrays before and during eltrombopag treatment. Median age was 78 years (range, 35–87 years); median baseline platelet count was 14 × 109/L (range, 2–68 × 109/L). Ten patients responded to the therapy, two cases relapsed after an initial response and the remaining two were refractory to the therapy. Eltrombopag induced relevant changes in the hematopoiesis, platelet activation and degranulation, as well as in megakaryocyte differentiation, with overexpression of some transcription factors and the genes PPBP, ITGB3, ITGA2B, F13A1, F13A1, MYL9 and ITGA2B. In addition, GP1BA, PF4, ITGA2B, MYL9, HIST1H4H and HIST1H2BH, genes regulated by RUNX1 were also significantly enriched after eltrombopag therapy. Furthermore, in non-responder patients, an overexpression of Bcl-X gene and genes involved in erythropoiesis, such as SLC4A1 and SLC25A39, was also observed. To conclude, overexpression in genes involved in megakaryopoiesis, platelet adhesion, degranulation and aggregation was observed in patients treated with eltrombopag. Moreover, an important role regarding heme metabolism was also present in non-responder patients.http://dx.doi.org/10.1080/09537104.2019.1702156immune thrombocytopeniapharmacogenomicstranscriptomic analysis |
| spellingShingle | Jesús María Hernández-Sánchez José María Bastida Diego Alonso-López Rocío Benito José Ramón González-Porras Javier De Las Rivas Jesús María Hernández Rivas Ana Eugenia Rodríguez-Vicente Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag Platelets immune thrombocytopenia pharmacogenomics transcriptomic analysis |
| title | Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| title_full | Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| title_fullStr | Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| title_full_unstemmed | Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| title_short | Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| title_sort | transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag |
| topic | immune thrombocytopenia pharmacogenomics transcriptomic analysis |
| url | http://dx.doi.org/10.1080/09537104.2019.1702156 |
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