We have confirmed the high incidence of DNMT3A mutations in patients with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often and have inferior OS when only patients achieving CR are analyzed. 'Double-mutated' patients have a very poor prognosis.

Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B*07, B*18, and B*40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein.

No abstract

Renowned international experts in higher education fi nancing have argued that, owing to large government defi cits, tertiary education will not be able to open up and meet growing demand unless cost-sharing principles and effi cient student fi nancial aid programmes are introduced. Opponents of cost-sharing in higher education object that introducing tuition fees will raise inequality in access to higher education. Drawing on OECD data, and focusing on college expectations, the authors argue that the effects of ability, gender, and socioeconomic background on college expectations are primarily shaped by the characteristics of secondary education systems, such as the degree of stratifi cation and vocational specifi city of secondary schools, while the principal characteristics of the tertiary education system, such as enrolment rates and the model of fi nancing, play a much less important role. The results clearly show that, after controlling for the effects of secondary school system characteristics, cost-sharing, as such or by degree, does not affect the formation of college expectations by ability, gender, and socioeconomic background as much as the selectivity of the secondary school system does.

The data in this research highlight significant differences in emergence times of permanent teeth due to the influence of BMI in Czech children. These findings are important for dental treatment planning.