ABSTRACT
To clarify the cooperative roles of recurrently identified mutations and to establish a more precise risk classification system in acute myeloid leukemia (AML), we comprehensively analyzed mutations in 51 genes, as well as cytogenetics and 11 chimeric transcripts, in 197 adult patients with de novo AML who were registered in the Japan Adult Leukemia Study Group AML201 study. We identified a total of 505 mutations in 44 genes, while only five genes, FLT3, NPM1, CEBPA, DNMT3A and KIT, were mutated in more than 10% of the patients. Although several cooperative and exclusive mutation patterns were observed, the accumulated mutation number was higher in cytogenetically normal AML and lower in AML with RUNX1-RUNX1T1 and CBFB-MYH11, indicating a strong potential of these translocations for the initiation of AML. Furthermore, we evaluated the prognostic impacts of each sole mutation and the combinations of mutations and/or cytogenetics, and demonstrated that AML patients could be clearly stratified into five risk groups for overall survival by including the mutation status of DNMT3A, MLL-PTD and TP53 genes in the risk classification system of the European LeukemiaNet. These results indicate that the prognosis of AML could be stratified by the major mutation status in combination with cytogenetics.
Subject(s)
Leukemia, Myeloid, Acute/genetics , Mutation , Adolescent , Adult , CCAAT-Enhancer-Binding Proteins/genetics , Cytogenetics , Disease-Free Survival , Humans , Karyotype , Leukemia, Myeloid, Acute/mortality , Middle Aged , Nucleophosmin , Prognosis , Proto-Oncogene Proteins c-kit/genetics , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
A cohort of 117 school children infected with Schistosoma haematobium was followed-up after therapy with praziquantel (0, 2, 4, 6, 12, and 18 months) and various infection and morbidity parameters (egg counts, hematuria, soluble egg antigen [SEA] in urine, and ultrasonography-detectable pathology) were quantified. At the onset of the study, 97% of the children were positive for S. haematobium with a geometric mean egg count of 45.7 eggs/10 ml of urine. Eighty-one percent of the children were positive for SEA in urine with a geometric mean SEA concentration of 218.8 ng/ml of urine. Ninety-two percent and 56% of the children were microhematuria positive and macrohematuria positive, respectively. Two months after treatment, all infection and morbidity indicators had significantly decreased. Reinfection after treatment as determined by detection of eggs in urine was observed by four months post-treatment while the other parameters remained low. The clearance of SEA was slower than that of egg counts while pathology resolved at an even slower pace. Levels of SEA and egg output showed similar correlations with ultrasound detectable pathology; these correlations were better than the correlation between hematuria and pathology.
Subject(s)
Antigens, Helminth/urine , Hematuria/drug therapy , Praziquantel/therapeutic use , Schistosoma haematobium , Schistosomiasis haematobia/drug therapy , Schistosomicides/therapeutic use , Adolescent , Animals , Child , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kenya/epidemiology , Male , Parasite Egg Count , Prevalence , Schistosoma haematobium/immunology , Schistosomiasis haematobia/epidemiology , Schistosomiasis haematobia/pathology , Schistosomiasis haematobia/urineABSTRACT
We evaluated the impact of praziquantel therapy (40 mg/kg body weight) on indicators of infection with Schistosoma haematobium by following a cohort of infected children from schools located 12 km apart in the Coast province of Kenya, at 0, 2, 4, 6, 12 and 18 months after treatment. Within this period, measurements of infection parameters pertaining to egg counts and haematuria (micro-, macro- and history) were evaluated at all time points. The initial prevalence of 100% dropped significantly 8 weeks after treatment with a similar trend in the intensity of infection. Microhaematuria followed the same trend as observed for egg counts while macrohaematuria remained low after treatment. Reinfection following successful therapy differed significantly between schools; in one school the children were reinfected immediately while those in the other remained uninfected despite similar starting prevalences, intensities of infection and cure rates. Transmission between the two areas looked homogeneous before treatment but when both groups were treated, contrasting transmission patterns became evident. In a regression model we evaluated factors that might be associated with reinfection, and after allowing for pretreatment infection level, age and sex, area (school) remained a highly significant predictor.
