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Clinical significance of genetic aberrations in secondary acute myeloid leukemia
Author(s) -
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,
Dvorakova Dana,
Robesova Blanka,
Wieser Rotraud,
Koller Elisabeth,
Suvajdzic Nada,
Tomin Dragica,
Tosic Natasa,
Colinge Jacques,
Racil Zdenek,
Steurer Michael,
Pavlovic Sonja,
Cazzola Mario,
Kralovics Robert
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23309
Subject(s) - myeloid leukemia , medicine , myeloid , clinical significance , oncology , immunology
The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High‐resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome‐Wide Human SNP 6.0 arrays. Genes TP53 , 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 (targeting CUX1 locus) 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 (14.3% ± 9.4% vs. 35.4% ± 7.2%; P = 0.002), 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 = 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. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.