Germline mutations in ETV6 are associated with
thrombocytopenia, red cell macrocytosis and predisposition to
lymphoblastic leukemia

J 2015

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia

NOETZLI, Leila, Richard W. LO, Alisa B. LEE-SHERICK, Michael CALLAGHAN, Patrizia NORIS et. al.

Základní údaje

Originální název

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia

Autoři

NOETZLI, Leila (840 Spojené státy), Richard W. LO (124 Kanada), Alisa B. LEE-SHERICK (840 Spojené státy), Michael CALLAGHAN (840 Spojené státy), Patrizia NORIS (380 Itálie), Anna SAVOIA (380 Itálie), Madhvi RAJPURKAR (840 Spojené státy), Kenneth JONES (840 Spojené státy), Katherine GOWAN (840 Spojené státy), Carlo L. BALDUINI (380 Itálie), Alessandro PECCI (380 Itálie), Chiara GNAN (380 Itálie), Daniela DE ROCCO (380 Itálie), Michael DOUBEK (203 Česká republika, garant, domácí), Ling LI (124 Kanada), Lily LU (124 Kanada), Richard LEUNG (124 Kanada), Carolina LANDOLT-MARTICORENA (124 Kanada), Stephen HUNGER (840 Spojené státy), Paula HELLER (32 Argentina), Arthur GUTIERREZ-HARTMANN (840 Spojené státy), Xiayuan LIANG (840 Spojené státy), Fred G. PLUTHERO (124 Kanada), Jesse W. ROWLEY (840 Spojené státy), Andrew S. WEYRICH (840 Spojené státy), Walter H.A. KAHR (124 Kanada), Christopher C. PORTER (840 Spojené státy) a Paola DI JORGE (840 Spojené státy)

Vydání

Nature genetics, New York, Nature Publishing Group, 2015, 1061-4036

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 31.616

Kód RIV

RIV/00216224:14110/15:00083395

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1038/ng.3253

UT WoS

000353635800018

EID Scopus

2-s2.0-84929130522

Klíčová slova anglicky

acute lymphoblastic leukemia; alternative RNA splicing; amino acid substitution;

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 7. 2015 17:19, Soňa Böhmová

Anotace

V originále

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia(1,2). We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.

Citovat

NOETZLI, Leila, Richard W. LO, Alisa B. LEE-SHERICK, Michael CALLAGHAN, Patrizia NORIS, Anna SAVOIA, Madhvi RAJPURKAR, Kenneth JONES, Katherine GOWAN, Carlo L. BALDUINI, Alessandro PECCI, Chiara GNAN, Daniela DE ROCCO, Michael DOUBEK, Ling LI, Lily LU, Richard LEUNG, Carolina LANDOLT-MARTICORENA, Stephen HUNGER, Paula HELLER, Arthur GUTIERREZ-HARTMANN, Xiayuan LIANG, Fred G. PLUTHERO, Jesse W. ROWLEY, Andrew S. WEYRICH, Walter H.A. KAHR, Christopher C. PORTER a Paola DI JORGE. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nature genetics. New York: Nature Publishing Group, 2015, roč. 47, č. 5, s. "535"-"U143", 6 s. ISSN 1061-4036. Dostupné z: https://dx.doi.org/10.1038/ng.3253.

@article{1306299,
   author = {Noetzli, Leila and Lo, Richard W. and LeeandSherick, Alisa B. and Callaghan, Michael and Noris, Patrizia and Savoia, Anna and Rajpurkar, Madhvi and Jones, Kenneth and Gowan, Katherine and Balduini, Carlo L. and Pecci, Alessandro and Gnan, Chiara and De Rocco, Daniela and Doubek, Michael and Li, Ling and Lu, Lily and Leung, Richard and LandoltandMarticorena, Carolina and Hunger, Stephen and Heller, Paula and GutierrezandHartmann, Arthur and Liang, Xiayuan and Pluthero, Fred G. and Rowley, Jesse W. and Weyrich, Andrew S. and Kahr, Walter H.A. and Porter, Christopher C. and Di Jorge, Paola},
   article_location = {New York},
   article_number = {5},
   doi = {http://dx.doi.org/10.1038/ng.3253},
   keywords = {acute lymphoblastic leukemia; alternative RNA splicing; amino acid substitution;},
   language = {eng},
   issn = {1061-4036},
   journal = {Nature genetics},
   title = {Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia},
   volume = {47},
   year = {2015}
}

TY  - JOUR
ID  - 1306299
AU  - Noetzli, Leila - Lo, Richard W. - Lee-Sherick, Alisa B. - Callaghan, Michael - Noris, Patrizia - Savoia, Anna - Rajpurkar, Madhvi - Jones, Kenneth - Gowan, Katherine - Balduini, Carlo L. - Pecci, Alessandro - Gnan, Chiara - De Rocco, Daniela - Doubek, Michael - Li, Ling - Lu, Lily - Leung, Richard - Landolt-Marticorena, Carolina - Hunger, Stephen - Heller, Paula - Gutierrez-Hartmann, Arthur - Liang, Xiayuan - Pluthero, Fred G. - Rowley, Jesse W. - Weyrich, Andrew S. - Kahr, Walter H.A. - Porter, Christopher C. - Di Jorge, Paola
PY  - 2015
TI  - Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia
JF  - Nature genetics
VL  - 47
IS  - 5
SP  - "535"-"U143"
EP  - "535"-"U143"
PB  - Nature Publishing Group
SN  - 10614036
KW  - acute lymphoblastic leukemia
KW  - alternative RNA splicing
KW  - amino acid substitution;
N2  - Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia(1,2). We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.
ER  -

NOETZLI, Leila, Richard W. LO, Alisa B. LEE-SHERICK, Michael CALLAGHAN, Patrizia NORIS, Anna SAVOIA, Madhvi RAJPURKAR, Kenneth JONES, Katherine GOWAN, Carlo L. BALDUINI, Alessandro PECCI, Chiara GNAN, Daniela DE ROCCO, Michael DOUBEK, Ling LI, Lily LU, Richard LEUNG, Carolina LANDOLT-MARTICORENA, Stephen HUNGER, Paula HELLER, Arthur GUTIERREZ-HARTMANN, Xiayuan LIANG, Fred G. PLUTHERO, Jesse W. ROWLEY, Andrew S. WEYRICH, Walter H.A. KAHR, Christopher C. PORTER a Paola DI JORGE. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. \textit{Nature genetics}. New York: Nature Publishing Group, 2015, roč.~47, č.~5, s.~''535''-''U143'', 6 s. ISSN~1061-4036. Dostupné z: https://dx.doi.org/10.1038/ng.3253.

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