Informace o publikaci

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

Autoři	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
Rok publikování	2012
Druh	Článek v odborném periodiku
Časopis / Zdroj	American Journal of Hematology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1002/ajh.23309
Obor	Onkologie a hematologie
Klíčová slova	gene mutation; acute myeloid leukemia
Přiložené soubory	AJH_Clinical_significance.pdf
Popis	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.