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

• Autoři: 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: Středoevropský technologický institut
• 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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