Functional analysis of germlineETV6 W380Rmutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia

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STAŇO KOZUBÍK Kateřina RADOVÁ Lenka RÉBLOVÁ Kamila ŠMÍDA Michal KUBRICANOVA ZALIOVA Marketa BALOUN Jiří PEŠOVÁ Michaela VRZALOVÁ Zuzana FOLBER František MEJSTŘÍKOVÁ Soňa POSPÍŠILOVÁ Šárka DOUBEK Michael

Rok publikování 2021
Druh Článek v odborném periodiku
Časopis / Zdroj Platelets
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://www.tandfonline.com/doi/full/10.1080/09537104.2020.1802416
Doi http://dx.doi.org/10.1080/09537104.2020.1802416
Klíčová slova Acute lymphoblastic leukemia; ETV6; myeloproliferative neoplasm; second hit
Popis Germline mutations inETV6gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation ofETV6W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET).In-silicoanalysis 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 germlineETV6mutation, ET probably started with somaticJAK2V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1IKZF1gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis.
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