Clinical significance of genetic aberrations in secondary acute
myeloid leukemia

J 2012

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

MILOSEVIC, Jelena D., Ana PUDA, Luca MALCOVATI, Tiina BERG, Michael HOFBAUER et. al.

Základní údaje

Originální název

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

Autoři

MILOSEVIC, Jelena D. (40 Rakousko), Ana PUDA (40 Rakousko), Luca MALCOVATI (380 Itálie), Tiina BERG (40 Rakousko), Michael HOFBAUER (40 Rakousko), Alexey STUKALOV (40 Rakousko), Thorsten KLAMPFL (40 Rakousko), Ashot S. HARUTYUNYAN (40 Rakousko), Heinz GISSLINGER (40 Rakousko), Bettina GISSLINGER (40 Rakousko), Tatiana BURJANIVOVA (703 Slovensko), Elisa RUMI (380 Itálie), Daniela PIETRA (380 Itálie), Chiara ELENA (380 Itálie), Alessandro M. VANNUCCHI (380 Itálie), Michael DOUBEK (203 Česká republika, domácí), Dana DVOŘÁKOVÁ (203 Česká republika, domácí), Blanka ROBEŠOVÁ (203 Česká republika, domácí), Rotraud WIESER (40 Rakousko), Elisabeth KOLLER (40 Rakousko), Nada SUVAJDZIC (191 Chorvatsko), Dragica TOMIN (191 Chorvatsko), Natasa TOSIC (191 Chorvatsko), Jacques COLINGE (40 Rakousko), Zdeněk RÁČIL (203 Česká republika, domácí), Michael STEURER (40 Rakousko), Sonja PAVLOVIC (191 Chorvatsko), Mario CAZZOLA (380 Itálie) a Robert KRALOVICS (40 Rakousko, garant)

Vydání

American Journal of Hematology, Hoboken, Wiley Periodicals, Inc. 2012, 0361-8609

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: 4.138

Kód RIV

RIV/00216224:14110/12:00060868

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1002/ajh.23309

UT WoS

000310246100013

Klíčová slova anglicky

gene mutation; acute myeloid leukemia

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 4. 2013 15:58, Soňa Böhmová

Anotace

V originále

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in AQ1 comparison with AML arising de novo (dnAML) and assess their impact on patients’ overall survival (OS). Genes TP53, AQ2 RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33–5.37; P 5 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms.

Přiložené soubory

AJH_Clinical_significance.pdf

Požádat o autorskou verzi souboru

Citovat

MILOSEVIC, Jelena D., Ana PUDA, Luca MALCOVATI, Tiina BERG, Michael HOFBAUER, Alexey STUKALOV, Thorsten KLAMPFL, Ashot S. HARUTYUNYAN, Heinz GISSLINGER, Bettina GISSLINGER, Tatiana BURJANIVOVA, Elisa RUMI, Daniela PIETRA, Chiara ELENA, Alessandro M. VANNUCCHI, Michael DOUBEK, Dana DVOŘÁKOVÁ, Blanka ROBEŠOVÁ, Rotraud WIESER, Elisabeth KOLLER, Nada SUVAJDZIC, Dragica TOMIN, Natasa TOSIC, Jacques COLINGE, Zdeněk RÁČIL, Michael STEURER, Sonja PAVLOVIC, Mario CAZZOLA a Robert KRALOVICS. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. American Journal of Hematology. Hoboken: Wiley Periodicals, Inc., 2012, roč. 87, č. 11, s. 1010-1016. ISSN 0361-8609. Dostupné z: https://dx.doi.org/10.1002/ajh.23309.

@article{991813,
   author = {Milosevic, Jelena D. and Puda, Ana and Malcovati, Luca and Berg, Tiina and Hofbauer, Michael and Stukalov, Alexey and Klampfl, Thorsten and Harutyunyan, Ashot S. and Gisslinger, Heinz and Gisslinger, Bettina and Burjanivova, Tatiana and Rumi, Elisa and Pietra, Daniela and Elena, Chiara and Vannucchi, Alessandro M. and Doubek, Michael and Dvořáková, Dana and Robešová, Blanka and Wieser, Rotraud and Koller, Elisabeth and Suvajdzic, Nada and Tomin, Dragica and Tosic, Natasa and Colinge, Jacques and Ráčil, Zdeněk and Steurer, Michael and Pavlovic, Sonja and Cazzola, Mario and Kralovics, Robert},
   article_location = {Hoboken},
   article_number = {11},
   doi = {http://dx.doi.org/10.1002/ajh.23309},
   keywords = {gene mutation; acute myeloid leukemia},
   language = {eng},
   issn = {0361-8609},
   journal = {American Journal of Hematology},
   title = {Clinical significance of genetic aberrations in secondary acute myeloid leukemia},
   volume = {87},
   year = {2012}
}

TY  - JOUR
ID  - 991813
AU  - Milosevic, Jelena D. - Puda, Ana - Malcovati, Luca - Berg, Tiina - Hofbauer, Michael - Stukalov, Alexey - Klampfl, Thorsten - Harutyunyan, Ashot S. - Gisslinger, Heinz - Gisslinger, Bettina - Burjanivova, Tatiana - Rumi, Elisa - Pietra, Daniela - Elena, Chiara - Vannucchi, Alessandro M. - Doubek, Michael - Dvořáková, Dana - Robešová, Blanka - Wieser, Rotraud - Koller, Elisabeth - Suvajdzic, Nada - Tomin, Dragica - Tosic, Natasa - Colinge, Jacques - Ráčil, Zdeněk - Steurer, Michael - Pavlovic, Sonja - Cazzola, Mario - Kralovics, Robert
PY  - 2012
TI  - Clinical significance of genetic aberrations in secondary acute myeloid leukemia
JF  - American Journal of Hematology
VL  - 87
IS  - 11
SP  - 1010-1016
EP  - 1010-1016
PB  - Wiley Periodicals, Inc.
SN  - 03618609
KW  - gene mutation
KW  - acute myeloid leukemia
N2  - The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in AQ1 comparison with AML arising de novo (dnAML) and assess their impact on patients’ overall survival (OS). Genes TP53, AQ2 RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33–5.37; P 5 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms.
ER  -

MILOSEVIC, Jelena D., Ana PUDA, Luca MALCOVATI, Tiina BERG, Michael HOFBAUER, Alexey STUKALOV, Thorsten KLAMPFL, Ashot S. HARUTYUNYAN, Heinz GISSLINGER, Bettina GISSLINGER, Tatiana BURJANIVOVA, Elisa RUMI, Daniela PIETRA, Chiara ELENA, Alessandro M. VANNUCCHI, Michael DOUBEK, Dana DVOŘÁKOVÁ, Blanka ROBEŠOVÁ, Rotraud WIESER, Elisabeth KOLLER, Nada SUVAJDZIC, Dragica TOMIN, Natasa TOSIC, Jacques COLINGE, Zdeněk RÁČIL, Michael STEURER, Sonja PAVLOVIC, Mario CAZZOLA a Robert KRALOVICS. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. \textit{American Journal of Hematology}. Hoboken: Wiley Periodicals, Inc., 2012, roč.~87, č.~11, s.~1010-1016. ISSN~0361-8609. Dostupné z: https://dx.doi.org/10.1002/ajh.23309.

Přehled o publikaci