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1.
Blood Cancer J ; 14(1): 57, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594285

ABSTRACT

In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification.


Subject(s)
Myelodysplastic Syndromes , Neoplasms , Humans , Retrospective Studies , Consensus , Prognosis , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/genetics , World Health Organization
2.
Blood Cancer J ; 14(1): 15, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38253683

ABSTRACT

Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPAbZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPAbZIP-inf. One hundred and thirteen CEBPAbZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPAbZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPAbZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPAbZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control.


Subject(s)
Leukemia, Myeloid, Acute , Adult , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Gene Expression Profiling , Mutation , Progression-Free Survival , Metabolic Networks and Pathways , CCAAT-Enhancer-Binding Proteins/genetics , NADPH Dehydrogenase
3.
J Clin Apher ; 38(5): 582-589, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37325919

ABSTRACT

BACKGROUND: The PLASMIC score was developed for distinguishing thrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy. However, two components of the PLASMIC score, mean corpuscular volume (MCV) and international normalized ratio (INR), showed non-significant differences between TTP and non-TTP patients in previous validations. Here, we validate the PLASMIC score and aim to modify it by adjusting the criteria of MCV and INR. MATERIALS AND METHODS: A retrospective validation of suspected TTP patients was performed by reviewing electronic medical records from two medical centers in Taiwan. The performance of different modified types of the PLASMIC score was carried out. RESULTS: Among 50 patients included in the final analysis, 12 were diagnosed with TTP based on deficiency of ADAMTS13 activity and clinical judgement. When stratified by high (score ≥ 6) and low-intermediate risk (score < 6), the positive predictive value (PPV) of the PLASMIC score to predict TTP was 0.45 (95% confidence interval [CI]: 0.29-0.61). The area under curve (AUC) was 0.70 (95% CI: 0.56-0.82). When adjusting the criteria of the PLASMIC score from MCV < 90 fL to MCV ≥ 90 fL, the PPV increased to 0.57 (95% CI: 0.37-0.75). The AUC was 0.75 (95% CI: 0.61-0.87). When adjusting the INR from >1.5 to >1.1, the PPV increased to 0.56 (95% CI: 0.39-0.71). The AUC was 0.81 (95% CI: 0.68-0.90). CONCLUSION: MCV ≥ 90 fL and/or INR > 1.1 might be suitable modifications for PLASMIC score but should be validated in a larger sample size.


Subject(s)
Purpura, Thrombotic Thrombocytopenic , Thrombotic Microangiopathies , Humans , Purpura, Thrombotic Thrombocytopenic/diagnosis , International Normalized Ratio , Retrospective Studies , Erythrocyte Indices , Thrombotic Microangiopathies/diagnosis , ADAMTS13 Protein
4.
Oncologist ; 25(9): 793-802, 2020 09.
Article in English | MEDLINE | ID: mdl-32275807

ABSTRACT

BACKGROUND: Patients with diffuse large B-cell lymphoma (DLBCL) with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear. MATERIALS AND METHODS: We conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016. RESULTS: Among 416 analyzed patients, 98 (23.6%) were HBsAg positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, p = .043), poorer 5-year overall survival (OS) rate (57.2% vs. 73.5%, p < .001), and shorter 5-year progression-free survival (PFS) rate (47.2% vs. 60.7%, p = .013). Multivariate analyses showed that HBsAg positivity was an independent unfavorable prognostic indicator for OS and PFS. A scoring system incorporating HBsAg positivity, the NCCN-IPI score, and serum albumin levels proved to be useful for stratifying prognostically relevant subgroups of patients with DLBCL. CONCLUSION: This study demonstrated that HBV infection is uniquely relevant to DLBCL. HBsAg might serve as a novel biomarker to improve clinical risk stratification of patients with DLBCL in areas with high prevalence of HBV infection. Further research investigating the etiopathogenesis of HBV infection in DLBCL is imperative. IMPLICATIONS FOR PRACTICE: A considerable disparity exists regarding the prognostic relevance of hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection in patients with diffuse large B-cell lymphoma (DLBCL). In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era.


Subject(s)
Hepatitis B Surface Antigens , Lymphoma, Large B-Cell, Diffuse , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Hepatitis B Surface Antigens/therapeutic use , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Vincristine/therapeutic use
5.
Nanotechnology ; 28(12): 125604, 2017 Mar 24.
Article in English | MEDLINE | ID: mdl-28220757

ABSTRACT

This paper describes the preparation of fluorinated graphene nanosheets (FGNs) through photoexfoliation of fluorinated graphite (FG) in the liquid phase. We discovered that UV irradiation of FG dispersions in N-methyl-2-pyrolidone facilitated exfoliation to give FGNs. Transmission electron microscopy and atomic force microscopy revealed that the average thickness of the FGNs was approximately 3 nm; they were considerably thinner than the nanosheets prepared using a conventional sonication approach. Furthermore, when the FGNs were deposited uniformly onto substrates (through spin coating), they formed effective cathode interlayers for polymer solar cells (PSCs), the efficiency of which was 60% greater than that of PSCs containing FGNs prepared through ultrasonication.

6.
J Hematol Oncol ; 9(1): 78, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27585840

ABSTRACT

BACKGROUND: Risk stratification based on cytogenetics of acute myeloid leukemia (AML) remains imprecise. The introduction of novel genetic and epigenetic markers has helped to close this gap and increased the specificity of risk stratification, although most studies have been conducted in specific AML subpopulations. In order to overcome this limitation, we used a genome-wide approach in multiple AML populations to develop a robust prediction model for AML survival. METHODS: We conducted a genome-wide expression analysis of two data sets from AML patients enrolled into the AMLCG-1999 trial and from the Tumor Cancer Genome Atlas (TCGA) to develop a prognostic score to refine current risk classification and performed a validation on two data sets of the National Taiwan University Hospital (NTUH) and an independent AMLCG cohort. RESULTS: In our training set, using a stringent multi-step approach, we identified a small three-gene prognostic scoring system, named Tri-AML score (TriAS) which highly correlated with overall survival (OS). Multivariate analysis revealed TriAS to be an independent prognostic factor in all tested training and additional validation sets, even including age, current cytogenetic-based risk stratification, and three other recently developed expression-based scoring models for AML. CONCLUSIONS: The Tri-AML score allows robust and clinically practical risk stratification for the outcome of AML patients. TriAS substantially refined current ELN risk stratification assigning 44.5 % of the patients into a different risk category.


Subject(s)
Leukemia, Myeloid, Acute/genetics , Risk Assessment/methods , Aged , Aged, 80 and over , Cytogenetics , Female , Genomics , Humans , Information Storage and Retrieval/methods , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/diagnosis , Male , Prognosis , Supervised Machine Learning , Survival Rate
7.
Oncotarget ; 6(36): 39098-110, 2015 Nov 17.
Article in English | MEDLINE | ID: mdl-26517675

ABSTRACT

Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of 158 de novo CN AML patients. We compared the gene expression profiles of patients with poor response to induction chemotherapy with those who responded well. Forty-six genes expressed differentially between the two groups. Among them, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P < 0.001) in ours and another 3 validation cohorts. In addition, it was an independent unfavorable prognostic factor by multivariate analysis (HR 1.116, 95% CI 1.035~1.204, P = 0.004). In conclusion, we developed a simple mRNA expression signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients.


Subject(s)
Leukemia, Myeloid, Acute/genetics , RNA, Messenger/biosynthesis , Female , Humans , Karyotyping , Leukemia, Myeloid, Acute/metabolism , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , Survival Analysis
8.
ACS Appl Mater Interfaces ; 7(13): 7397-405, 2015 Apr 08.
Article in English | MEDLINE | ID: mdl-25786137

ABSTRACT

Metal nanostructures that trigger plasmonic near-field effects are often incorporated in organic photovoltaic devices (OPVs) to improve their light-harvesting ability. These nanostructures usually can be positioned in two different locations in a device: (i) within the photon absorption layers and (ii) at the interfaces between the active layer and the metal electrodes. In this study, we developed amphiphilic gold nanoparticles (Au NPs) for use in dual plasmonic nanostructures within OPVs. We employed graphene oxide as the template to anchor the Au NPs, thereby avoiding their aggregation. Furthermore, we added poly(ethylene glycol) (PEG) bis(amine) to the synthesis medium to improve the solubility of the nanocomposites, such that they could be dispersed well in water and in several organic solvents. Accordingly, we could incorporate the PEGylated Au NP/graphene oxides readily into both the buffer layer and photoactive layer of OPVs, which, as a result, exhibited obvious enhancements in their photocurrents and overall device efficiencies. Moreover, we observed different spectral enhancement regions when we positioned the nanocomposites at different locations, reflecting the different dielectric environments surrounding the NPs; this unexpected behavior should assist in enhancing the broadband absorption of solar irradiation.

9.
Materials (Basel) ; 8(8): 5414-5425, 2015 Aug 21.
Article in English | MEDLINE | ID: mdl-28793513

ABSTRACT

Atomically thin two-dimensional (2D) transition metal dichalcogenides have also attracted immense interest because they exhibit appealing electronic, optical and mechanical properties. In this work, we prepared gold nanoparticle-decorated molybdenum sulfide (AuNP@MoS2) through a simple spontaneous redox reaction. Transmission electron microscopy, UV-Vis spectroscopy, and Raman spectroscopy were used to characterize the properties of the AuNP@MoS2 nanomaterials. Then we employed such nanocomposites as the cathode buffer layers of organic photovoltaic devices (OPVs) to trigger surface plasmonic resonance, leading to noticeable enhancements in overall device efficiencies. We attribute the primary origin of the improvement in device performance to local field enhancement induced by the effects of localized surface plasmonic resonance. Our results suggest that the metal nanoparticle-decorated two-dimensional materials appear to have great potential for use in high-performance OPVs.

10.
Nanoscale ; 6(3): 1573-9, 2014.
Article in English | MEDLINE | ID: mdl-24326523

ABSTRACT

In this work, gold nanoparticle/graphene oxide (AuNP/GO) nanocomposites are synthesized and used as anodic buffer layers in organic photovoltaic devices (OPVs). The application of thiol-terminated polyethylene glycol as a capping agent prevents the aggregation of AuNPs on the GO surface and further improves the solubility and stability of these nanomaterials in solutions. When AuNP/GO nanomaterials served as the buffer layers, they introduced localized surface plasmon resonance (LSPR) in the OPVs, leading to noticeable enhancements in the photocurrent and the efficiencies of the OPVs. We attribute the primary origin of the improvement in device performance to local field enhancement induced by the LSPR. We anticipate that this study might open up new avenues for constructing plasmon-enhancing layers on the nanoscale to improve the performance of solar cells.

11.
ACS Appl Mater Interfaces ; 5(23): 12419-24, 2013 Dec 11.
Article in English | MEDLINE | ID: mdl-24229393

ABSTRACT

Solution-processed nanocomposites containing molybdenum oxide (MoO3) and gold nanoparticles (Au NPs) have been used as anode buffer layers in organic photovoltaic devices (OPVs). The resulting devices exhibit a remarkable enhancement in power conversion efficiency after Au NPs were incorporated into the device. Such enhancements can be attributed to the localized surface plasmon resonance induced by the metallic nanostructures. We have also found that the rate of exciton generation and the probability of exciton dissociation were increased. Furthermore, the devices made of the MoO3 buffer layer containing Au NPs exhibited superior stability. This work opens up the possibility of fabricating OPVs with both high efficiency and a prolonged lifetime.

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