XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy
Abstract Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological...
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| Format: | Article |
| Language: | English |
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BMC
2017-02-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-017-0412-4 |
| _version_ | 1811274159711322112 |
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| author | Vincent Camus Hadjer Miloudi Antoine Taly Brigitte Sola Fabrice Jardin |
| author_facet | Vincent Camus Hadjer Miloudi Antoine Taly Brigitte Sola Fabrice Jardin |
| author_sort | Vincent Camus |
| collection | DOAJ |
| description | Abstract Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies. Recent reports have shown molecular alterations in the gene encoding XPO1 and showed a mutation hotspot (E571K) in the following two hematological malignancies with similar phenotypes and natural histories: primary mediastinal diffuse large B cell lymphoma and classical Hodgkin’s lymphoma. Emerging evidence suggests that the mutant XPO1 E571K plays a role in carcinogenesis, and this variant is quantifiable in tumor and plasma cell-free DNA of patients using highly sensitive molecular biology techniques, such as digital PCR and next-generation sequencing. Therefore, it was proposed that the XPO1 E571K variant may serve as a minimal residual disease tool in this setting. To clarify and summarize the recent findings on the role of XPO1 in B cell hematological malignancies, we conducted a literature search to present the major publications establishing the landscape of XPO1 molecular alterations, their impact on the XPO1 protein, their interest as biomarkers, and investigations into the development of new XPO1-targeted therapies in B cell hematological malignancies. |
| first_indexed | 2024-04-12T23:14:01Z |
| format | Article |
| id | doaj.art-6ccf03c084ff4e41bec3b03f995422b6 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-12T23:14:01Z |
| publishDate | 2017-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-6ccf03c084ff4e41bec3b03f995422b62022-12-22T03:12:44ZengBMCJournal of Hematology & Oncology1756-87222017-02-0110111310.1186/s13045-017-0412-4XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapyVincent Camus0Hadjer Miloudi1Antoine Taly2Brigitte Sola3Fabrice Jardin4Normandie Univ, INSERM U1245, UNICAEN, UNIROUENNormandie Univ, INSERM U1245, UNICAEN, UNIROUENLaboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS, Université Paris DiderotNormandie Univ, INSERM U1245, UNICAEN, UNIROUENNormandie Univ, INSERM U1245, UNICAEN, UNIROUENAbstract Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies. Recent reports have shown molecular alterations in the gene encoding XPO1 and showed a mutation hotspot (E571K) in the following two hematological malignancies with similar phenotypes and natural histories: primary mediastinal diffuse large B cell lymphoma and classical Hodgkin’s lymphoma. Emerging evidence suggests that the mutant XPO1 E571K plays a role in carcinogenesis, and this variant is quantifiable in tumor and plasma cell-free DNA of patients using highly sensitive molecular biology techniques, such as digital PCR and next-generation sequencing. Therefore, it was proposed that the XPO1 E571K variant may serve as a minimal residual disease tool in this setting. To clarify and summarize the recent findings on the role of XPO1 in B cell hematological malignancies, we conducted a literature search to present the major publications establishing the landscape of XPO1 molecular alterations, their impact on the XPO1 protein, their interest as biomarkers, and investigations into the development of new XPO1-targeted therapies in B cell hematological malignancies.http://link.springer.com/article/10.1186/s13045-017-0412-4XPO1ExportinLymphomaTargeted therapyMinimal residual disease |
| spellingShingle | Vincent Camus Hadjer Miloudi Antoine Taly Brigitte Sola Fabrice Jardin XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy Journal of Hematology & Oncology XPO1 Exportin Lymphoma Targeted therapy Minimal residual disease |
| title | XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy |
| title_full | XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy |
| title_fullStr | XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy |
| title_full_unstemmed | XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy |
| title_short | XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy |
| title_sort | xpo1 in b cell hematological malignancies from recurrent somatic mutations to targeted therapy |
| topic | XPO1 Exportin Lymphoma Targeted therapy Minimal residual disease |
| url | http://link.springer.com/article/10.1186/s13045-017-0412-4 |
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