[Clinical Significance of Truncated Mutant ΔJBP of TET2 Gene in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPAdm) were more frequency (31.3% vs 0, P=0.009), the complete remission (CR) rate after induction chemotherapy(37.5% vs 81.8%, P=0.008) were lower, the median EFS (5 vs 19 months, P=0.000) and median OS (16 vs 22 months, P=0.041) were shorter. Univariate analysis showed that platelets <50×109/L (P=0.004) and CEBPAdm (P=0.001) were related to the shorter OS of the patients. Further COX multivariate analysis showed that CEBPAdm is an independent prognostic factors of OS in TET2ΔJBP patients (P=0.010). In addition, ΔJBP patients with CEBPAdm showed lower hemoglobin levels (62 vs 75g/L, P=0.030) and lower median OS (9 months vs 18 months, P=0.000) than the patients without CEBPAdm. CONCLUSION: AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPAdm, which is the independent prognostic factors of OS in AML patients with TET2ΔJBP.

Bipolar resistance switching characteristics in TiN/ZnO:Mn/Pt junctions developed for nonvolatile resistive memory application.

As conventional flash memory is approaching its fundamental scaling limit, there is an urgent demand for an alternative nonvolatile memory technology at present. Resistance-switching random access memory has attracted extensive interests due to its nonvolatile nature, good scalability, and simple structure. In this work, TiN/ZnO:Mn/Pt junctions, which employ a conductive compound TiN as the top electrode to replace regular metal electrodes, were fabricated and investigated for nonvolatile resistive memory applications. These junctions exhibit bistable resistance state at room temperature, and the devices can be reproducibly switched between the two resistance states by applying bidirectional voltage biases. Moreover, both resistance states are demonstrated to retain for more than 10(4) s without electrical power, demonstrating a nonvolatile nature of the memory device. The mechanism of resistance switching effects in TiN/ZnO:Mn/Pt junctions is interpreted in terms of the drift of oxygen vacancies and the resultant formation/annihilation of local conductive channels through ZnO:Mn/Pt Schottky barrier.

Fully room-temperature-fabricated nonvolatile resistive memory for ultrafast and high-density memory application.

Through a simple industrialized technique which was completely fulfilled at room temperature, we have developed a kind of promising nonvolatile resistive switching memory consisting of Ag/ZnO:Mn/Pt with ultrafast programming speed of 5 ns, an ultrahigh R(OFF)/R(ON) ratio of 10(7), long retention time of more than 10(7) s, good endurance, and high reliability at elevated temperatures. Furthermore, we have successfully captured clear visualization of nanoscale Ag bridges penetrating through the storage medium, which could account for the high conductivity in the ON-state device. A model concerning redox reaction mediated formation and rupture of Ag bridges is therefore suggested to explain the memory effect. The Ag/ZnO:Mn/Pt device represents an ultrafast and highly scalable (down to sub-100-nm range) memory element for developing next generation nonvolatile memories.