[Effect of FLT3-ITD Length on 32D Cell Proliferation, Apoptosis and Sensitivity to FLT3 Inhibitor].

OBJECTIVE: To study the effects of FLT3-ITD length on 32D cell proliferation, apoptosis and sensitivity to FLT3 inhibitor, so as to provide references for stepwise therapy of FLT3-ITD mutated acute myeloid leukemia patients. METHODS: Three different FLT3-ITD mutants with same or adjacent insert sites were selected and constructed in an eukaryotic expression vector. FLT3-ITD mutants stably expressed 32D cell strains were selected with the help of lentivirus system and IL3 free cell culture medium. The proliferation and apoptosis of 32D cell strains after AC220 treatment were detected. RESULTS: FLT3-ITD mutants (ITD1, ITD2 and ITD3) stably expressed 32D cell strains were constructed successfully. In the absence of IL3 factor, the proliferation number of ITD1, ITD2 and ITD3 cell strains were mounted up to 2.3 folds, 3.7 folds, and 4.3 folds after 48 hours, respectively. Under the exposure of FLT3 inhibitor AC220, the IC50 values was 0.183, 0.446 and 0.836 nmol/L, and apoptosis rates was 88.6%, 34.2% and 16.1%, respectively. CONCLUSION: FLT3-ITD mutant expressed cell strains with longer ITD show higher capacity of proliferation and higher tolerance to AC220 treatment.

Improving cadmium mobilization by phosphate-solubilizing bacteria via regulating organic acids metabolism with potassium.

Organic acids secreted by phosphorus-solubilizing bacteria (PSB) is one of the main biological metabolites with cadmium (Cd) mobilization capacity in the conversion of insoluble precipitate forms to bioavailable forms in contaminated soil. However, the fluctuating concentrations of nutrient elements caused by agricultural activities may result in the substantial variances of carbohydrate metabolism of microorganisms involved in Cd remediation, it is therefore essential to study how metabolic strategies, especially for organic acids, affected by the environmentally friendly fertilizers, such as potassium (K). In this study, adding K+ (KCl) concentrations from 0.0 to 100.0 mg/L in medium clearly accelerated Cd mobilization from 15.9 to 35.9 mg/L via inducing the secretion of tartaric acid, 3-hydroxybutyrate, fumaric and succinic acids, increased by 10.0-, 7.5-, 4.3- and 4.1-fold changes, respectively. Current data revealed that the significant differences of metabolic pathways and genes expressions with the varied K+ concentrations included: ⅰ) K+ induces a substantial up-regulation in metabolic pathway of pyruvic acid to oxaloacetate and tartaric acids; ⅱ) the varied expression of genes involved in encoding enzymes of tricarboxylic acid cycle result in the up-regulated fumaric acid, succinic acid and 3-hydroxybutyrate; ⅲ) the expression of genes related enzyme cysteine and glutamate metabolism processes promoted with the increasing bioavailable Cd concentrations. Besides, P-type ATPase activity increased with K+ levels, indicating that H+ efflux and medium acidification were strengthened. In general, an appropriate enhancement of K based fertilizer is an effective manner for soil Cd remediation via the regulation of organic acids metabolism and H+ secretion of PSB.

Role of SIRT1 in hematologic malignancies.

Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.