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

J 2021

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

STAŇO KOZUBÍK, Kateřina, Lenka RADOVÁ, Kamila RÉBLOVÁ, Michal ŠMÍDA, Marketa KUBRICANOVA ZALIOVA et. al.

Basic information

Original name

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

Authors

STAŇO KOZUBÍK, Kateřina (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), Michal ŠMÍDA (203 Czech Republic, belonging to the institution), Marketa KUBRICANOVA ZALIOVA (203 Czech Republic), Jiří BALOUN (203 Czech Republic, belonging to the institution), Michaela PEŠOVÁ (203 Czech Republic, belonging to the institution), Zuzana VRZALOVÁ (203 Czech Republic, belonging to the institution), František FOLBER (203 Czech Republic, belonging to the institution), Soňa MEJSTŘÍKOVÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Michael DOUBEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Platelets, PHILADELPHIA, TAYLOR & FRANCIS INC, 2021, 0953-7104

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.236

RIV identification code

RIV/00216224:14740/21:00120094

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1080/09537104.2020.1802416

UT WoS

000561184900001

Keywords in English

Acute lymphoblastic leukemia; ETV6; myeloproliferative neoplasm; second hit

Abstract

V originále

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.

Links

MUNI/A/1395/2019, interní kód MU

Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VII (Acronym: VýDiTeHeMa VII)

Investor: Masaryk University, Category A

NU20-08-00137, research and development project

Name: Vyhledávání a funkční testování variant genů predisponujících k familiárním onemocněním krvetvorby

Investor: Ministry of Health of the CR, Searching and functional testing of gene variants predisposing to familial haematopoietic disorders, Subprogram 1 - standard

Citovat

STAŇO KOZUBÍK, Kateřina, Lenka RADOVÁ, Kamila RÉBLOVÁ, Michal ŠMÍDA, Marketa KUBRICANOVA ZALIOVA, Jiří BALOUN, Michaela PEŠOVÁ, Zuzana VRZALOVÁ, František FOLBER, Soňa MEJSTŘÍKOVÁ, Šárka POSPÍŠILOVÁ and Michael DOUBEK. Functional analysis of germlineETV6 W380Rmutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia. Platelets. PHILADELPHIA: TAYLOR & FRANCIS INC, 2021, vol. 32, No 6, p. 838-841. ISSN 0953-7104. Available from: https://dx.doi.org/10.1080/09537104.2020.1802416.

@article{1765766,
   author = {Staňo Kozubík, Kateřina and Radová, Lenka and Réblová, Kamila and Šmída, Michal and Kubricanova Zaliova, Marketa and Baloun, Jiří and Pešová, Michaela and Vrzalová, Zuzana and Folber, František and Mejstříková, Soňa and Pospíšilová, Šárka and Doubek, Michael},
   article_location = {PHILADELPHIA},
   article_number = {6},
   doi = {http://dx.doi.org/10.1080/09537104.2020.1802416},
   keywords = {Acute lymphoblastic leukemia; ETV6; myeloproliferative neoplasm; second hit},
   language = {eng},
   issn = {0953-7104},
   journal = {Platelets},
   title = {Functional analysis of germlineETV6 W380Rmutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia},
   url = {https://www.tandfonline.com/doi/full/10.1080/09537104.2020.1802416},
   volume = {32},
   year = {2021}
}

TY  - JOUR
ID  - 1765766
AU  - 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
PY  - 2021
TI  - Functional analysis of germlineETV6 W380Rmutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia
JF  - Platelets
VL  - 32
IS  - 6
SP  - 838-841
EP  - 838-841
PB  - TAYLOR & FRANCIS INC
SN  - 09537104
KW  - Acute lymphoblastic leukemia
KW  - ETV6
KW  - myeloproliferative neoplasm
KW  - second hit
UR  - https://www.tandfonline.com/doi/full/10.1080/09537104.2020.1802416
N2  - 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.
ER  -

STAŇO KOZUBÍK, Kateřina, Lenka RADOVÁ, Kamila RÉBLOVÁ, Michal ŠMÍDA, Marketa KUBRICANOVA ZALIOVA, Jiří BALOUN, Michaela PEŠOVÁ, Zuzana VRZALOVÁ, František FOLBER, Soňa MEJSTŘÍKOVÁ, Šárka POSPÍŠILOVÁ and Michael DOUBEK. Functional analysis of germlineETV6 W380Rmutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia. \textit{Platelets}. PHILADELPHIA: TAYLOR \&{} FRANCIS INC, 2021, vol.~32, No~6, p.~838-841. ISSN~0953-7104. Available from: https://dx.doi.org/10.1080/09537104.2020.1802416.

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