Chromothripsis in myeloid malignancies.

Chromothripsis refers to massive genomic rearrangements developed during a catastrophic event. In total acute myeloid leukemia (AML), the incidence of chromothripsis ranges from 0 to 6.6%, in cases of complex karyotype AML, the incidence of chromothripsis ranges from 27.3 to 100%, whereas in cases of AML with TP53 mutations, the incidence ranges from 11.1 to 90%. For other types of malignancies, the incidence of chromothripsis also varies, from 0 to 10.5% in myelodysplastic syndrome to up to 61.5% in cases of myelodysplastic syndrome with TP53 mutations.Chromothripsis is typically associated with complex karyotypes and TP53 mutations, and monosomal karyotypes are associated with the condition. ERG amplifications are frequently noted in cases of chromothripsis, whereas MYC amplifications are not. Moreover, FLT3 and NPM1 mutations are negatively associated with chromothripsis. Chromothripsis typically occurs in older patients with AML with low leukocyte counts and bone marrow blast counts. Rare cases of patients with chromothripsis who received intensive induction chemotherapy revealed low response rates and poor overall prognosis. Signal pathways in chromothripsis typically involve copy number gain and upregulation of oncogene gene sets that promote cancer growth and a concomitant copy number loss and downregulation of gene sets associated with tumor suppression functions.Patients with chromothripsis showed a trend of lower complete remission rate and worse overall survival in myeloid malignancy. Large-scale studies are required to further elucidate the causes and treatments of the condition.

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.

BACKGROUND: We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia. METHODS: miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests. RESULTS: Cognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Video Abstract CONCLUSION: Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.

Emerging impacts of ionic liquids on eco-environmental safety and human health.

Owing to their unique physicochemical properties, ionic liquids (ILs) have been rapidly applied in diverse areas, such as organic synthesis, electrochemistry, analytical chemistry, functional materials, pharmaceutics, and biomedicine. The increase in the production and application of ILs has resulted in their release into aquatic and terrestrial environments. Because of their low vapor pressure, ILs cause very little pollution in the atmosphere compared to organic solvents. However, ILs are highly persistent in aquatic and terrestrial environments due to their stability, and therefore, potentially threaten the safety of eco-environments and human health. Specifically, the environmental translocation and retention of ILs, or their accumulation in organisms, are all related to their physiochemical properties, such as hydrophobicity. Based on results of ecotoxicity, cytotoxicity, and toxicity in mammalian models, the mechanisms involved in IL-induced toxicity include damage of cell membranes and induction of oxidative stress. Recently, artificial intelligence and machine learning techniques have been used in mining and modeling toxicity data to make meaningful predictions. Major future challenges are also discussed. This review will accelerate our understanding of the safety issues of ILs and serve as a guideline for the design of the next generation of ILs.

Hyperspectral sensing of heavy metals in soil by integrating AI and UAV technology.

Given the limitation of conventional soil pollution monitoring through mapping which is a costly, time-consuming work, the study aims to establish an image recognition model to identify the source of pollution automatically. The study choses a contaminated land and then use a non-destructive instrument that can quickly and effectively measure the content of heavy metals. A two concentration prediction models of Ni, Cu, Zn, Cr, Pb, As, Cd, and Hg using hyperspectral imaging were developed, Decision Tree and Back Propagation Neural Network, in combination of particle swarm optimization employed for optimization algorithm. As a result, random forest is more accurate than the forecast result of back propagation neural network. This study has established an excellent Cu and Cr model, which can accurately capture the pollution source. In addition, through aerial photographs, we also found that there were also high pollution reactions on the banks of the river. The developed model is beneficial for high pollution areas which can be quickly found, thereby following investigation and remediation work can be carried out with less time and cost consuming comparing with the conventional soil monitoring.

Structural Engineering and Optimization of Zwitterionic Salts for Expeditious Discovery of Thermoresponsive Materials.

This work reported the discovery of N-triflimide (NTf)-based zwitter-ionic liquids (ZILs) that exhibit UCST-type phase transitions in water, and their further structural optimization in fine-tuning polarity to ultimately afford newfangled thermosensitive materials carrying attractive and biocompatible Tc values that clearly demonstrated the true value of the tunability of ZIL structure. This research established that with non-aromatic, acyclic ZILs as small-molecule thermoresponsive materials, their mixing and de-mixing with water triggered by temperatures are entirely reversible.

Using an unmanned aerial system to monitor and assess irrigation water channels susceptible to sediment deposition.

The irrigation channel of the Qishan River is among the most crucial agricultural water resource facilities in Qishan District, Kaohsiung City, Taiwan. The channel was blocked by debris due to flood events caused by Typhoon Morakot in 2009. This study analyzed images captured by an unmanned aerial system to identify channel areas susceptible to sediment deposition and propose measures for reducing the effects of natural hazards on irrigation water resources. The analysis results revealed that the channel was located downstream of the Qishan River; however, debris flows, riverbank landslides, and natural dam breaches deposited sediment in the downstream section, preventing the flow of water. Furthermore, the sediment and driftwood blocked the channel. The channel was also blocked due to a hyperconcentrated flow. Sediment deposition areas and volumes were estimated. On the basis of these results, we suggest that the damaged riverbed groundsills and river tributary banks be restored to inhibit erosion. In addition, subsurface water collection and transfer structures should be constructed to maintain the flow of water during the dry season. The study findings are expected to increase the efficiency of agricultural irrigation water management and prevent natural hazards from affecting water resources.

Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS. METHODS: shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance. RESULTS: Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P <  0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group. CONCLUSIONS: This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.

Chronic disseminated candidiasis manifesting as hepatosplenic abscesses among patients with hematological malignancies.

BACKGROUND: The outcomes of deep-seated abscesses attributed to chronic disseminated candidiasis (CDC) in patients with hematological malignancies have rarely been reported in recent years. METHODS: We retrospectively reviewed and analyzed the data of patients with hematological malignancies who received a diagnosis of CDC at a medical center in Taiwan between 2008 and 2013. RESULTS: Sixty-one patients (32 men and 29 women) were diagnosed with CDC. The median age was 51 years (range: 18-83). The overall incidence of CDC was 1.53 per 100 patient-years in patients with hematological malignancies between 2008 and 2013. The highest incidence of CDC was 4.3 per 100 patient-years for acute lymphoblastic leukemia, followed by 3.6 for acute myeloid leukemia. We detected 3 (4.9%) proven, 13 (21.3%) probable, and 45 (73.8%) possible cases of CDC. A total of 13 patients had positive blood cultures for Candida species: C. tropicalis (8), C. albicans (2), C. glabrata (2), and C. famata (1). The median duration of antifungal treatment was 96 days (range: 7-796 days). Serial imaging studies revealed that the resolution rate of CDC was 30.0% at 3 months and 54.3% at 6 months. Five patients (8.2%) had residual lesions that persisted beyond one year. A multivariate analysis of the 90-day outcome revealed that shock was the only independent prognostic factor of 90-day survival in patients with CDC. CONCLUSION: The incidence of CDC did not decrease between 2008 and 2013. Patients with acute leukemia had a higher risk of CDC than those with other hematological malignancies. Imaging studies conducted at 6 months after diagnosis revealed that only half of the patients showed complete resolution. CDC requires prolonged treatment, and serial imaging at 6 months interval is suggested. Shock is the only independent prognostic factor of 90-day survival in patients with CDC.

Reaction-Based Detection of Chemical Warfare Agent Mimics with Affinity Ionic Liquids.

We are demonstrating here the successful development of an ionic liquid device based on affinity ionic liquids AIL 1-6 tailored for chemoselective detection of gaseous chemical warfare agent (CWA) mimics on a quartz crystal microbalance (QCM) as well as on disposable filter papers. In the QCM platform, the negligible vapor pressure of ionic liquids ensures that AILs do not dry out on quartz chips and are used free of leakage during the measurements. This lack of vapor pressure makes these ionic liquid devices highly attractive for gas analysis. In the present study, chemoselective CWA mimic vapor detection by QCM occurs when gas rapidly diffuses into the AIL thin film and accordingly the nucleophilic substitution reaction emerges under the experimental conditions developed. Our initial results give credence to three important conclusions: (i) AILs could be prepared in short synthetic steps and are remarkable in detecting CWA mimics, (ii) the analysis of gaseous CWA mimics on QCM is label-free and chemoselective, and (iii) the detection of CWA mimic vapor by AILs on filter paper discs is colorimetric and portable, and, once used, the paper disc can be disposed. To the best of our knowledge, this is the first report in the literature based on the CWA mimic vapor detection in ionic liquids on a QCM.

Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor-risk factor in de novo acute myeloid leukemia patients.

OBJECTIVES: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited. METHODS: A total of 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications. RESULTS: Hyperleukocytosis, defined as initial white blood cell counts above 50 000/µL, occurred in 28.9% of AML patients. HL patients had higher incidences of FLT3-ITD, NPM1, DNMT3A, CEBPA, and TET2 mutations. Multivariate analysis demonstrated that HL was an independent poor prognostic factor for overall survival and disease-free survival in total patients, those with intermediate-risk cytogenetics and normal karyotype irrespective of genetic alterations. Intriguingly, HL predicted poor survival in CEBPA double mutated, NPM1 + /FLT3-ITD- and NPM1-/FLT3-ITD- patients. Further, HL patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR) had a significantly longer overall survival and disease-free survival than those without allo-HSCT. CONCLUSIONS: Hyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo-HSCT in first CR seems to ameliorate the poor prognostic impact of HL.

Hepatitis B reactivation among 1962 patients with hematological malignancy in Taiwan.

BACKGROUND: The risk of Hepatitis B virus (HBV) reactivation in patients with different hematological malignancy except lymphoma were rarely known before. METHODS: A total of 1962 patients with hematological malignancy were enrolled and followed-up at the National Taiwan University Hospital between 2008 and 2013. The clinical characteristics, HBV serology, and laboratory data were retrospectively reviewed and analyzed. RESULTS: A total of 1962 patients comprising 1048 men and 914 women were studied. The median age of the patients was 55 years (range, 15-97 years). Chronic HBV carriage was documented at diagnosis of hematological malignancy in 286 (14.6%) patients. A total of 171 (59.8%) of the 286 HBV carriers received primary prophylaxis with anti-HBV agents. Of the HBV carriers, 97 (33.9%) developed hepatitis B reactivation during or after chemotherapy, including 59 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among patients with hematological malignancy and HBV carriage was 10.4 per 100 person-years. A multivariate analysis revealed hepatocellular carcinoma (p < 0.001) and antiviral prophylaxis use (p < 0.001) were independent risk factors of HBV reactivation in HBV carriers. Of the 1676 patients with initial negative hepatitis B surface antigen (HBsAg) counts, 41 (2.4%) experienced hepatitis B reactivation, reverse seroconversion of HBsAg, and lost their protective hepatitis B surface antibody (anti-HBs). A multivariate analysis revealed that diabetes mellitus (p = 0.005, odds ratio (OR): 0.218, 95% confidence interval (CI): 0.076-0.629), allogeneic transplantation (p = 0.013, OR: 0.182, 95% CI: 0.047-0.701), liver cirrhosis (p < 0.001, OR: 0.002, 95% CI: 0-0.047), low anti-HBs titers (p = 0.016, OR: 0.020, 95% CI: 0.001-0.480), and positive hepatitis B core antibody (p = 0.013, OR: 0.070, 95% CI: 0.009-0.571) were independent risk factors of positive seroconversion of HBsAg in patients with hematological malignancy. CONCLUSIONS: The incidence of HBV reactivation among the patients with varying subtypes of hematological malignancy is similar. Prophylaxis with anti-HBV agents critically reduced the risk of hepatitis B reactivation.

Thermal monitoring and analysis of the large-scale field earth-dam breach process.

Thermal imaging is a nondestructive testing method for monitoring internal material changes that are indicated by changes in an object's surface temperature. In this study, field observation using thermographs was applied to monitor and analyze the breach process of large-scale earth dams. The earth dam test site was Landao Creek in Nantou County, Taiwan. Four field tests were performed to monitor and analyze a single earth dam and two successive earth dams. Ponding first occurred at the lowland of the riverbed upstream, and base seepage occurred at the base of the dam downstream; overtopping failure soon followed. Earth-dam failure mode is affected by the topographic characteristics of the riverbed; specifically, lowland areas are prone to ponding upstream, which causes piping and seepage downstream as well as subsequent breaches. Ponding and piping cause water seepage and soil wetting, which are reflected in lower surface temperatures recorded on thermographs. Thermographs can monitor changes in surface temperature to evaluate the potential failure modes of dams. Dam surfaces with large temperature variations may be potential failure areas. If confirmed, this fact may prove useful for failure-mode prediction. This paper proposes a monitoring index to reflect the temperature changes in a given period, and this study verified it empirically.

microRNA let-7g suppresses PDGF-induced conversion of vascular smooth muscle cell into the synthetic phenotype.

Platelet-derived growth factor (PDGF) can promote vascular smooth muscle cells (VSMCs) to switch from the quiescent contractile phenotype to synthetic phenotype, which contributes to atherosclerosis. We aimed to investigate the role of microRNA let-7g in phenotypic switching. Bioinformatics prediction was used to find let-7g target genes in the PDGF/mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/Krüppel-like factor-4 (KLF4) signalling pathway that affects VSMC phenotypic switching. The luciferase reporter assay and let-7g transfection were used to confirm let-7g target genes. Two contractile proteins alpha-smooth muscle actin (α-SMA) and calponin were VSMC-specific genes and were measured as the indicators for VSMC phenotype. Lentivirus carrying the let-7g gene was injected to apolipoprotein E knockout (apoE-/- ) mice to confirm let-7g's effect on preventing atherosclerosis. Through the PDGF/MEKK1/ERK/KLF4 signalling pathway, PDGF-BB can inhibit α-SMA and calponin. The PDGFB and MEKK1 genes were predicted to harbour let-7g binding sites, which were confirmed by our reporter assays. Transfection of let-7g to VSMC also reduced PDGFB and MEKK1 levels. Moreover, we showed that let-7g decreased phosphorylated-ERK1/2 while had no effect on total ERK1/2. KLF4 can reduce VSMC-specific gene expression by preventing myocardin-serum response factor (SRF) complex from associating with these gene promoters. The immunoprecipitation assay showed that let-7g decreased the interaction between KLF4 and SRF. Further experiments demonstrated that let-7g can increase α-SMA and calponin levels to maintain VSMC in the contractile status. Injection of lentivirus carrying let-7g gene increased let-7g's levels in aorta and significantly decreased atherosclerotic plaques in the apoE-/- mice. We demonstrated that let-7g reduces the PDGF/MEKK1/ERK/KLF4 signalling to maintain VSMC in the contractile status, which further reduce VSMC atherosclerotic change.

Debris flow-induced topographic changes: effects of recurrent debris flow initiation.

Chushui Creek in Shengmu Village, Nantou County, Taiwan, was analyzed for recurrent debris flow using numerical modeling and geographic information system (GIS) spatial analysis. The two-dimensional water flood and mudflow simulation program FLO-2D were used to simulate debris flow induced by rainfall during typhoon Herb in 1996 and Mindulle in 2004. Changes in topographic characteristics after the debris flows were simulated for the initiation of hydrological characteristics, magnitude, and affected area. Changes in topographic characteristics included those in elevation, slope, aspect, stream power index (SPI), topographic wetness index (TWI), and hypsometric curve integral (HI), all of which were analyzed using GIS spatial analysis. The results show that the SPI and peak discharge in the basin increased after a recurrence of debris flow. The TWI was higher in 2003 than in 2004 and indicated higher potential of landslide initiation when the slope of the basin was steeper. The HI revealed that the basin was in its mature stage and was shifting toward the old stage. Numerical simulation demonstrated that the parameters' mean depth, maximum depth, affected area, mean flow rate, maximum flow rate, and peak flow discharge were increased after recurrent debris flow, and peak discharge occurred quickly.

Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides.

Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 1-3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides.

Clinical characteristics and treatment outcomes of patients with candidaemia due to Candida parapsilosis sensu lato species at a medical centre in Taiwan, 2000-12.

OBJECTIVES: To investigate the clinical characteristics and treatment outcomes of adult patients with Candida parapsilosis sensu lato candidaemia. METHODS: We evaluated data in the mycology database of the National Taiwan University Hospital and on patients diagnosed with candidaemia due to C. parapsilosis sensu lato species from 2000 to 2012. Isolates were identified to the species level by conventional identification methods, MALDI-TOF and gene sequencing analysis. RESULTS: A total of 323 adult patients with candidaemia caused by C. parapsilosis sensu lato species were evaluated, including 256 (79.3%) patients with C. parapsilosis sensu stricto, 34 (10.5%) with Candida orthopsilosis and 33 (10.2%) with Candida metapsilosis. There were 222 men and 101 women and the median age was 60 years (range 18-103 years). Among them, 178 (55%) had an underlying diagnosis of cancer. The overall 30 day mortality rate was 25% (n = 80). Multivariate analysis revealed that shock (P < 0.001), antifungal therapy (P = 0.002), central catheter removal (P = 0.02) and abdominal surgery (P = 0.043) were independent prognostic factors for patients with candidaemia due to C. parapsilosis sensu lato species. There were no significant differences in 30 day mortality rate among patients with candidaemia caused by the three different species (P = 0.770). All isolates of C. metapsilosis, C. orthopsilosis and C. parapsilosis sensu stricto were susceptible to voriconazole. WT isolates were susceptible to itraconazole, posaconazole and amphotericin B. CONCLUSIONS: There were no significant differences in 30 day mortality among patients with candidaemia caused by C. parapsilosis sensu stricto, C. metapsilosis or C. orthopsilosis. The currently used antifungal agents exhibited good in vitro activities against C. parapsilosis sensu lato species isolates.

Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia.

Alterations of galectin-3 expression are often seen in cancers and may contribute to tumorigenesis, cancer progression, and metastasis. The studies concerning clinical implications of galectin-3 expression in patients with acute myeloid leukemia (AML) are scarce. We investigated the expression of LGALS3, the gene encoding galectin-3, in the bone marrow (BM) mononuclear cells from an original cohort comprising 280 adults with primary non-acute promyelocytic leukemia. Higher LGALS3 expression was closely associated with older age, French-American-British M4/M5 subtypes, CD14 expression on leukemic cells, and PTPN11 mutation, but negatively correlated with CEBPA mutation and FLT3-ITD. Compared with patients with lower LGALS3 expression, those with higher expression had lower complete remission rates, higher primary refractory rates, and shorter overall survival. This result was validated in an independent validation cohort. A scoring system incorporating higher LGALS3 expression and 8 other risk factors, including age, white blood cell count, cytogenetics, and gene mutations, into survival analysis proved to be very useful to stratify patients with AML into different prognostic groups (P < .001). In conclusion, BM LGALS3 expression may serve as a new biomarker to predict clinical outcome in patients with AML, and galectin-3 may serve as a potential therapeutic target in those patients with higher expression of this protein.

Risk factors and clinical outcomes of acute myeloid leukaemia with central nervous system involvement in adults.

BACKGROUND: Acute myeloid leukaemia (AML) with central nervous system (CNS) involvement in adults is uncommon, and studies of this subject are scant. METHODS: We conducted a retrospective study to investigate the clinical aspects, cytogenetic abnormalities, molecular gene mutations and outcomes of adult AML patients with CNS involvement. Three hundred and ninety-five patients with newly diagnosed AML were reviewed. RESULTS: Twenty (5.1%) patients had CNS involvement, including 7 (1.8%) with initial CNS disease and 4 (1%) who suffered an isolated CNS relapse. The patients with CNS involvement were younger, had higher leukocyte, platelet, and peripheral blast cell counts, FAB M4 morphology, and chromosome translocations involving 11q23 (11q23 abnormalities) more frequently than did the patients without CNS involvement. No differences in sex, haemoglobin levels, serum LDH levels, immunophenotype of leukaemia cells, or molecular gene mutations were observed between the two groups. Multivariate analyses showed that age ≤ 45 years (OR, 5.933; 95% CI, 1.82 to 19.343), leukocyte counts ≥ 50,000/µl (OR, 3.136; 95% CI, 1.083 to 9.078), and the presence of 11q23 abnormalities (OR, 5.548; 95% CI, 1.208 to 25.489) were significant predictors of CNS involvement. Patients with initial CNS disease had 5-year overall survival and relapse-free survival rates that were similar to those without initial CNS disease. However, three of four patients who suffered an isolated CNS relapse died, and their prognosis was as poor as that of patients who suffered a bone marrow relapse. CONCLUSION: CNS involvement in adult patients with AML is rare. Three significant risk factors for CNS involvement including age ≤ 45 years, leukocyte counts ≥ 50,000/µl and the presence of 11q23 abnormalities were identified in this study. Future investigations to determine whether adult AML patients having these specific risk factors would benefit from CNS prophylactic therapy are necessary.

GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.

Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.7, and 1 % of patients with CEBPA (double-mut), CEBPA (single-mut), and CEBPA wild type, respectively. All but one patient with GATA2 mutation had concurrent CEBPA mutation. GATA2 mutations were closely associated with younger age, FAB M1 subtype, intermediate-risk cytogenetics, expression of HLA-DR, CD7, CD15, or CD34 on leukemic cells, and CEBPA mutation, but negatively associated with FAB M4 subtype, favorable-risk cytogenetics, and NPM1 mutation. Patients with GATA2 mutation had significantly better overall survival and relapse-free survival than those without GATA2 mutation. Sequential analysis showed that the original GATA2 mutations might be lost during disease progression in GATA2-mutated patients, while novel GATA2 mutations might be acquired at relapse in GATA2-wild patients. In conclusion, AML patients with GATA2 mutations had distinct clinic-biological features and a favorable prognosis. GATA2 mutations might be lost or acquired at disease progression, implying that it was a second hit in the leukemogenesis of AML, especially those with CEBPA mutation.

Exploring silver ionic liquids for reaction-based gas sensing on a quartz crystal microbalance.

Reaction-based, sensitive sensing of aldehyde and ketone gases in real time was effectively achieved on QCM chips thin-coated with silver ionic liquids and , respectively. The method platform developed in this work involves straightforward synthesis of functional silver ionic liquids in water, and is label-free and highly chemoselective with superior gas reactivity for and and, most significantly, totally insensitive to moisture.