[FLT3 Mutations in Acute Myeloid Leukemia].

FMS-like tyrosine kinase 3 (FLT3), a class III tyrosine kinase receptor, plays an important role in the pro- liferation, survival, and differentiation of hematopoietic stem/progenitor cells. Approximately 30% of pa- tients with cytogenetically normal acute myeloid leukemia (CN-AML) harbor FLT3 mutations. The most frequent FLT3 mutations are internal tandem duplications (ITDs) in the juxtamembrane domain. FLT3-ITD mutations cause ligand-independent dimerization of FLT3 and the constitutive activation of its downstream signaling pathways, such as PI3K/AKT, A4APK/ERK, and STAT5, leading to dysregulated cellular prolifera- tion. The relapse risk of CN-AML patients with FLT3-ITD is higher and the overall survival (OS) of such patients is shorter than those of patients with wild-type FLT3. Recently genome-wide studies with next-generation sequencing have suggested that mutational combinations of genes related to signal transduction, transcription, splicing, cancer suppressors, and epigenetics contribute to the pathogenesis of AML. These mutations including FLT3-ITD may be prognostic factors facilitating the risk stratification for CN-AML. The point mutations D835/I836 in the tyrosine kinase domain (TKD) are detected in 5-7% of AML patients. The clinical relevance of these FLT3-TKD mutations remains unclear. FLT3-TKD mutations are detected even in patients treated with FLT3 inhibitors as secondary mutations, suggesting that the mutations are as- sociated with the resistance. Therefore, the detection of these mutations might provide us with the opportunity to consider appropriate treatment for patients. The molecular abnormalities in AML patients give us insights into the pathology of AML and clinically significant information required for the diagnosis, prognosis, and treatment decisions. [Review].

Prevalence of Helicobacter pylori infection measured with urinary antibody in an urban area of Japan, 2008-2010.

Helicobacter pylori (H. pylori) has expanded to infect about half the world's population. Although there were many studies on the prevalence of H. pylori infection for defined areas in the 1990s throughout the world, there were only limited sources tracking its latest prevalence among large populations. In the present study, we estimated the prevalence of H. pylori among the inhabitants of Nagoya, an urban area of Japan. Study subjects were 5167 participants (1467 males and 3700 females) aged 35 to 69 years from the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). A urinary anti-H. pylori antibody was used to detect H. pylori infection. The history of eradication treatments for H. pylori infection was obtained using self-administered questionnaires. The prevalence detected by the urinary test included 19.6% (95% confidence interval; 16.8-22.6%) for those aged 35-39 years, 25.8% (23.5-28.2%) for 40-49 years, 39.4% (36.8-42.1%) for 50-59 years, 50.3% (47.8-52.7%) for 60-69 years, and 36.4% (35.1-37.7%). Among 5167 participants, 266 (5.1%) stated that they had received an eradication treatment. Since 167 subjects with negative urinary tests replied that they had been seropositive for H. pylori in the past, they were included among the ever-infected inhabitant group. Consequently, the overall rate of those with a history of persistent infection was 39.6% (38.3-40.9%). The prevalence of H. pylori infection observed in Nagoya seemed to be lower than the corresponding prevalence reported in other studies of Japan. That lower rate might be due to the reduced exposure from improved urban sanitary conditions.