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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3847-3853.
Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-08-3522.
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Submitted August 31, 2005
Accepted January 9, 2006
NRAS mutations in AML: biology, cytogenetics, and prognosis - a study on 2502 patients
Ulrike Bacher, Torsten Haferlach, Claudia Schoch, Wolfgang Kern, and Susanne Schnittger*
Department of Clinical Chemistry, University Hospital of Munich, Munich, Germany
MLL - Munich Leukemia Laboratory, Munich, Germany
* Corresponding author; email: susanne.schnittger{at}mll-online.de.
In the presented study we analyzed 2502 patients with acute myeloid leukemia at diagnosis for NRAS mutations around the hot spots at codon 12, 13, and 61. We correlated the results to cytomorphology, cytogenetics, other molecular markers and prognostic relevance of these mutations. 257/2502 pts. (10.3%) showed NRAS mutations. The majority of mutations was found at codon 12 (n=112/257; 43.6%), mostly resulting in changes from glycine to asparagine. The history of AML did not differ significantly in association to NRAS mutations. The subgroups with inv(16)/t(16;16) and inv(3)/t(3;3) showed a significantly higher frequency of NRASmut (50/133 (37.6%)(p< 0.0001) and 11/41 (26.8%) (p=0.0004), respectively) when compared to the total cohort. In addition, in these two subgroups mutations of codon 61 were significantly overrepresented (both p< 0.0001). In contrast NRASmut were significantly underrepresented in t(15;17) (2/102; 2.0%) (p=0.0048), in the subgroup with MLL/11q23 rearrangements (3/77; 3.9%) (p=0.0616), and in complex aberrant karyotype (4/258; 1.6%) (p< 0.0001). Overall we did not find a significant prognostic impact of NRASmut for OS, EFS and DFS. However, there was a trend to better survival in most subgroups especially when other molecular markers (FLT3-LM, MLL-PTD and NPM) were taken into account.
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