WT1 mutations are secondary events in AML, show varying frequencies and impact on prognosis between genetic subgroups

To investigate frequency and prognostic impact of Wilms tumor 1 ( WT1 ) mutations (mut), we analyzed 3157 unselected acute myeloid leukemia patients for WT1 mut in exons 7 and 9. In total, 188 WT1 mutations were detected (exon 7: n =150, exon 9: n =38); 141 were frameshift, 24 missense, 14 non-sense...

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Veröffentlicht in:	Leukemia 2015-03, Vol.29 (3), p.660-667
Hauptverfasser:	Krauth, M-T, Alpermann, T, Bacher, U, Eder, C, Dicker, F, Ulke, M, Kuznia, S, Nadarajah, N, Kern, W, Haferlach, C, Haferlach, T, Schnittger, S
Format:	Artikel
Sprache:	eng
Schlagworte:	38/88 45 45/23 631/208/737 631/67 631/67/1990 631/67/1990/283 692/699/67/1990/283/1897 692/700/1750 Acute myeloid leukemia Adolescent Adult Age Factors Aged Aged, 80 and over Antineoplastic Agents - therapeutic use Axons Cancer Cancer Research CCAAT-Enhancer-Binding Proteins - genetics Critical Care Medicine DNA (Cytosine-5-)-Methyltransferases - genetics Exons Female Females fms-Like Tyrosine Kinase 3 - genetics Gene Expression Regulation, Leukemic Gene mutations Genetic research Genetic susceptibility Health aspects Hematology Humans Intensive Internal Medicine Karyotypes Leukemia Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - pathology Male Males Medical prognosis Medicine Medicine & Public Health Middle Aged Multivariate analysis Mutation Myeloid leukemia Oncogene Proteins, Fusion - genetics Oncology Oncology, Experimental original-article Prognosis Repressor Proteins - genetics Sex differences Sex Factors Subgroups Survival Analysis WT1 protein WT1 Proteins - genetics
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Zusammenfassung:	To investigate frequency and prognostic impact of Wilms tumor 1 ( WT1 ) mutations (mut), we analyzed 3157 unselected acute myeloid leukemia patients for WT1 mut in exons 7 and 9. In total, 188 WT1 mutations were detected (exon 7: n =150, exon 9: n =38); 141 were frameshift, 24 missense, 14 non-sense, 7 splice site and 2 indel mutations. In 175/3157 (5.5%) patients, a WT1 mut was found. Higher frequencies were detected in patients with biallelic CEBPA mut (13.6%; P =0.001), followed by t(15;17)/ PML-RARA (11.0%, P =0.004), and FLT3 -ITD (8.5%, P
ISSN:	0887-6924 1476-5551
DOI:	10.1038/leu.2014.243