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SNP array analysis of acute promyelocytic leukemia may be of prognostic relevance and identifies a potential high risk group with recurrent deletions on chromosomal subband 1q31.3

To search for new copy number alterations (CNAs) in acute promyelocytic leukemia (APL), we analyzed DNA from leukemic blasts of 93 acute promyelocytic leukemia (APL) patients with Genome-Wide SNP 6.0 arrays (SNP-A). We identified 259 CNAs consisting of 170 heterozygous deletions, 82 amplifications,...

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Main Authors: Nowak, Daniel (Author) , Klaumünzer, Marion (Author) , Hanfstein, Benjamin (Author) , Mossner, Maximilian (Author) , Nolte, Florian (Author) , Nowak, Verena (Author) , Obländer, Julia (Author) , Hecht, Anna (Author) , Hütter, Gero (Author) , Seifarth, Wolfgang (Author) , Fabarius, Alice (Author) , Erben, Philipp (Author) , Saußele, Susanne (Author) , Müller, Martin Christian (Author) , Reiter, Andreas (Author) , Weiß, Christel (Author) , Hofmann, Wolf-Karsten (Author) , Lengfelder, Eva (Author)
Format: Article (Journal)
Language:English
Published: 9 April 2012
In: Genes, chromosomes & cancer
Year: 2012, Volume: 51, Issue: 8, Pages: 756-767
ISSN:1098-2264
DOI:10.1002/gcc.21961
Online Access:Resolving-System, Volltext: http://dx.doi.org/10.1002/gcc.21961
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.21961
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Author Notes:Daniel Nowak, Marion Klaumuenzer, Benjamin Hanfstein, Maximilian Mossner, Florian Nolte, Verena Nowak, Julia Oblaender, Anna Hecht, Gero Hütter, Seishi Ogawa, Alexander Kohlmann, Claudia Haferlach, Brigitte Schlegelberger, Jan Braess, Wolfgang Seifarth, Alice Fabarius, Philipp Erben, Susanne Saussele, Martin C. Müller, Andreas Reiter, Thomas Buechner, Christel Weiss, Wolf-Karsten Hofmann, and Eva Lengfelder
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Summary:To search for new copy number alterations (CNAs) in acute promyelocytic leukemia (APL), we analyzed DNA from leukemic blasts of 93 acute promyelocytic leukemia (APL) patients with Genome-Wide SNP 6.0 arrays (SNP-A). We identified 259 CNAs consisting of 170 heterozygous deletions, 82 amplifications, and 7 regions of copy number neutral loss of heterozygosity. One of the most common CNAs was a deletion on chromosomal subband 1q31.3 in 13 of 93 (14%) patients encompassing the coding regions for the microRNAs mir181a1/b1. In multivariable analysis with the covariates age, white blood cell count, platelet count, and FLT3-ITD/FLT3 D835 mutations we found that after adjustment for patients' age (P < 0.0001), patients with 2 or more CNAs detected by SNP-A had a higher risk of death (hazard ratio = 5.942, P = 0.0015) than patients with 0 or 1 CNA. Deletions of 1q31.3 were associated with a higher number of CNAs (median 2 vs. 8, P < 0.0001) and were a strong independent prognostic factor for an increased risk of relapse (hazard ratio = 28.9, P = 0.0031). This study presents a comprehensive assessment of new CNAs as pathomechanistically relevant targets and possible prognostic factors which could refine risk stratification of APL. © 2012 Wiley Periodicals, Inc.
Item Description:Gesehen am 01.08.2018
Physical Description:Online Resource
ISSN:1098-2264
DOI:10.1002/gcc.21961

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