Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia
Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thr...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-08-01
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| Series: | Platelets |
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| Online Access: | http://dx.doi.org/10.1080/09537104.2020.1802416 |
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| author | Katerina Stano Kozubik Lenka Radova Kamila Reblova Michal Smida Marketa Zaliova Kubricanova Jiri Baloun Michaela Pesova Zuzana Vrzalova Frantisek Folber Sona Mejstrikova Sarka Pospisilova Michael Doubek |
| author_facet | Katerina Stano Kozubik Lenka Radova Kamila Reblova Michal Smida Marketa Zaliova Kubricanova Jiri Baloun Michaela Pesova Zuzana Vrzalova Frantisek Folber Sona Mejstrikova Sarka Pospisilova Michael Doubek |
| author_sort | Katerina Stano Kozubik |
| collection | DOAJ |
| description | Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET). In-silico analysis predicted impaired DNA binding due to W380R mutation. Functional analysis showed that this mutation prevents the ETV6 protein from localizing into the cell nucleus and impairs the transcriptional repression activity of ETV6. Based on the germline ETV6 mutation, ET probably started with somatic JAK2 V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1 IKZF1 gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis. |
| first_indexed | 2024-03-12T00:26:39Z |
| format | Article |
| id | doaj.art-df06206cdabd4b8b86d66e3bdd0b8058 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:26:39Z |
| publishDate | 2021-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-df06206cdabd4b8b86d66e3bdd0b80582023-09-15T10:38:08ZengTaylor & Francis GroupPlatelets0953-71041369-16352021-08-0132683884110.1080/09537104.2020.18024161802416Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemiaKaterina Stano Kozubik0Lenka Radova1Kamila Reblova2Michal Smida3Marketa Zaliova Kubricanova4Jiri Baloun5Michaela Pesova6Zuzana Vrzalova7Frantisek Folber8Sona Mejstrikova9Sarka Pospisilova10Michael Doubek11Masaryk University (CEITEC MU)Masaryk University (CEITEC MU)Masaryk University (CEITEC MU)Masaryk University (CEITEC MU)Charles University in Prague and Motol University HospitalMasaryk University (CEITEC MU)Masaryk University (CEITEC MU)Masaryk University (CEITEC MU)Masaryk UniversityMasaryk University (CEITEC MU)Masaryk University (CEITEC MU)Masaryk University (CEITEC MU)Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET). In-silico analysis predicted impaired DNA binding due to W380R mutation. Functional analysis showed that this mutation prevents the ETV6 protein from localizing into the cell nucleus and impairs the transcriptional repression activity of ETV6. Based on the germline ETV6 mutation, ET probably started with somatic JAK2 V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1 IKZF1 gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis.http://dx.doi.org/10.1080/09537104.2020.1802416acute lymphoblastic leukemiaetv6myeloproliferative neoplasmsecond hit |
| spellingShingle | Katerina Stano Kozubik Lenka Radova Kamila Reblova Michal Smida Marketa Zaliova Kubricanova Jiri Baloun Michaela Pesova Zuzana Vrzalova Frantisek Folber Sona Mejstrikova Sarka Pospisilova Michael Doubek Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia Platelets acute lymphoblastic leukemia etv6 myeloproliferative neoplasm second hit |
| title | Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| title_full | Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| title_fullStr | Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| title_full_unstemmed | Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| title_short | Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| title_sort | functional analysis of germline etv6 w380r mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia |
| topic | acute lymphoblastic leukemia etv6 myeloproliferative neoplasm second hit |
| url | http://dx.doi.org/10.1080/09537104.2020.1802416 |
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