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.

Basic information

Original name

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

Authors

MILOSEVIC, Jelena D. (40 Austria), Ana PUDA (40 Austria), Luca MALCOVATI (380 Italy), Tiina BERG (40 Austria), Michael HOFBAUER (40 Austria), Alexey STUKALOV (40 Austria), Thorsten KLAMPFL (40 Austria), Ashot S. HARUTYUNYAN (40 Austria), Heinz GISSLINGER (40 Austria), Bettina GISSLINGER (40 Austria), Tatiana BURJANIVOVA (703 Slovakia), Elisa RUMI (380 Italy), Daniela PIETRA (380 Italy), Chiara ELENA (380 Italy), Alessandro M. VANNUCCHI (380 Italy), Michael DOUBEK (203 Czech Republic, belonging to the institution), Dana DVOŘÁKOVÁ (203 Czech Republic, belonging to the institution), Blanka ROBEŠOVÁ (203 Czech Republic, belonging to the institution), Rotraud WIESER (40 Austria), Elisabeth KOLLER (40 Austria), Nada SUVAJDZIC (191 Croatia), Dragica TOMIN (191 Croatia), Natasa TOSIC (191 Croatia), Jacques COLINGE (40 Austria), Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Michael STEURER (40 Austria), Sonja PAVLOVIC (191 Croatia), Mario CAZZOLA (380 Italy) and Robert KRALOVICS (40 Austria, guarantor)

Edition

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

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

Impact factor

Impact factor: 4.138

RIV identification code

RIV/00216224:14110/12:00060868

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000310246100013

Keywords in English

gene mutation; acute myeloid leukemia

Abstract

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.

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Cite

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 and Robert KRALOVICS. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. American Journal of Hematology. Hoboken: Wiley Periodicals, Inc., 2012, vol. 87, No 11, p. 1010-1016. ISSN 0361-8609. Available from: 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 and Robert KRALOVICS. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. \textit{American Journal of Hematology}. Hoboken: Wiley Periodicals, Inc., 2012, vol.~87, No~11, p.~1010-1016. ISSN~0361-8609. Available from: https://dx.doi.org/10.1002/ajh.23309.

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