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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Prochazka, KT; Pregartner, G; Rücker, FG; Heitzer, E; Pabst, G; Wölfler, A; Zebisch, A; Berghold, A; Döhner, K; Sill, H.
Clinical implications of subclonal TP53 mutations in acute myeloid leukemia.
Haematologica. 2019; 104(3):516-523
Doi: 10.3324/haematol.2018.205013
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- Leading authors Med Uni Graz
- Prochazka Katharina
- Sill Heinz
- Co-authors Med Uni Graz
- Berghold Andrea
- Heitzer Ellen
- Pabst Gabriel
- Pregartner Gudrun
- Wölfler Albert
- Zebisch Armin
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- Abstract:
- The role of subclonal TP53 mutations, defined by a variant allele frequency of <20%, has not been addressed in acute myeloid leukemia yet. We, therefore, analyzed their prognostic value in a cohort of 1,537 patients with newly diagnosed disease, prospectively treated within three trials of the "German-Austrian Acute Myeloid Leukemia Study Group". Mutational analysis was performed by targeted deep sequencing and patients with TP53 mutations were categorized by their variant allele frequency into groups with frequencies >40%, 20%-40% and <20%. A total of 108 TP53 mutations were found in 98 patients (6.4%). Among these, 61 patients had variant allele frequencies >40%, 19 had variant allele frequencies between 20%-40% and 18 had frequencies <20%. Compared to specimens with clonal TP53 mutations, those with subclonal ones showed significantly fewer complex karyotypes and chromosomal losses. In either TP53-mutated group, patients experienced significantly fewer complete responses (P<0.001) and had worse overall and event-free survival rates (P<0.0001). In Cox regression analyses adjusting for age, white blood cell count, cytogenetic risk and type of acute myeloid leukemia, the adverse prognostic effect of TP53 mutations remained significant for all TP53-mutated subgroups. These data suggest that subclonal TP53 mutations are a novel prognostic parameter in acute myeloid leukemia and emphasize the usefulness of next-generation sequencing technologies for risk stratification in this disorder. The study was registered at ClinicalTrials.gov with number NCT00146120. Copyright© 2019 Ferrata Storti Foundation.