Evaluation Of Different NPM1 Mutations In AML Patients According To Clinical, Cytogenetic and Molecular Features and Impact On Outcome
| Autor: | Christiane Eder, Torsten Haferlach, Susanne Schnittger, Alexander Kohlmann, Wolfgang Kern, Frank Dicker, Tamara Alpermann, Claudia Haferlach |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Blood. 122:51-51 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Background NPM1 mutations (NPM1mut) are known to be prognostically favorable in the absence of FLT3-ITD. About 80% of patients (pts) have previously been shown to carry a distinct NPM1mut (“type A”). The remaining NPM1mut pts show various rare mutations (“rare types”) with different individual frequencies. Whether these “rare types” differ from “type A” with respect to clinical outcome and accompanying genetic abnormalities is unknown. Aim To evaluate the incidence of “rare types” of NPM1mut in AML and to investigate whether they show differences in cytogenetics, concomitant molecular mutations, biological or prognostic profiles compared to pts with the common “type A”. Patients and Methods A cohort of 2,859 newly diagnosed adult AML pts were screened for NPM1mut by melting curve analysis and subsequent Sanger sequencing of the positive cases. In 877 (30.7%) pts NPM1mut were detected. All 877 NPM1mut pts were also analyzed for FLT3-ITD. The following markers were screened in the respective subcohorts: FLT3-TKD (n=869), MLL-PTD (n=872), WT1 (n=785), CEBPA (n=690), IDH2R172 (n=590), IDH1R132 (n=582), IDH2R140 (n=577), RUNX1 (n=531), DNMT3A (n=529), ASXL1 (n=432), NRAS (n=390), KRAS (n=231), and TET2 (n=216). Results In total, 660/877 (75.3%) mutations were “type A” mutations (c.860_863dupTCTG), whereas 217/877 (24.7%) represented “rare types”. The most common of the latter was type B (c.863_864insCATG; n=77; 8.8% of all NPM1mut) followed by type D (c.863_864insCCTG; n=56; 6.4%), and type I (c.863_864insCTTG; n=15; 1.7%). The remaining 41 types were present in less than 1% each. Pts with “rare types” were slightly younger than pts with “type A” (mean 61.4 yrs vs 63.8 yrs; p=0.035) and showed a trend for lower WBC counts (50.6 vs 61.2x109/L; p=0.051). Neither gender, hemoglobin level, platelet count, the history of the disease, the percentage of bone marrow blasts, normal vs aberrant karyotypes, nor distribution between the intermediate and adverse cytogenetic risk scores according to the refined MRC criteria varied between “rare types” and “type A”. “Rare types” more often harbored WT1 mutations than “type A” pts (10.6% vs 3.3%; p Conclusions 1) Rare NPM1mut types harbored more frequently WT1mut and less frequently DNMT3Amut. 2) The adverse effect of FLT3-ITD mutations within NPM1mut pts is not seen within the “rare types”, but only in those pts showing NPM1mut “type A”. 3) Therefore, NPM1mut pts showing “rare types” might not be stratified by their FLT3-ITD status, but by their prognostically favorable NPM1mut only. Disclosures: Alpermann: MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. |
| Databáze: | OpenAIRE |
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