Global burden of anticancer drug-induced acute kidney injury and tubulointerstitial nephritis from 1967 to 2023.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

Fasting blood glucose and the risk of all-cause mortality in patients with diabetes mellitus undergoing hemodialysis.

BACKGROUND: Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking. METHODS: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality. RESULTS: Patients with FBG 80-100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04-1.17), 1.21 (95% CI, 1.13-1.29), 1.36 (95% CI, 1.26-1.46), and 1.61 (95% CI, 1.51-1.72) for patients with FBG 100-125, 125-150, 150-180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG <80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05-1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased. CONCLUSION: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80-100 mg/dL in HD patients with DM.

Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling.

Complex karyotype (CK) is associated with a poor prognosis in both acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB). Transcriptomic analyses have improved our understanding of the disease and risk stratification of myeloid neoplasms; however, CK-specific gene expression signatures have been rarely investigated. In this study, we developed and validated a CK-specific gene expression signature. Differential gene expression analysis between the CK and non-CK groups using data from 348 patients with AML and MDS-EB from four cohorts revealed enrichment of the downregulated genes localized on chromosome 5q or 7q, suggesting that haploinsufficiency due to the deletion of these chromosomes possibly underlies CK pathogenesis. We built a robust transcriptional model for CK prediction using LASSO regression for gene subset selection and validated it using the leave-one-out cross-validation method for fitting the logistic regression model. We established a 10-gene CK signature (CKS) predictive of CK with high predictive accuracy (accuracy 94.22%; AUC 0.977). CKS was significantly associated with shorter overall survival in three independent cohorts, and was comparable to that of previously established risk stratification models for AML. Furthermore, we explored of therapeutic targets among the genes comprising CKS and identified the dysregulated expression of superoxide dismutase 1 (SOD1) gene, which is potentially amenable to SOD1 inhibitors.

Implications of the 5th Edition of the World Health Organization Classification and International Consensus Classification of Myeloid Neoplasm in Myelodysplastic Syndrome With Excess Blasts and Acute Myeloid Leukemia.

The fifth edition of the WHO classification (2022 WHO) and the International Consensus Classification (2022 ICC) of myeloid neoplasms have been recently published. We reviewed the changes in the diagnosis distribution in patients with MDS with excess blasts (MDS-EB) or AML using both classifications. Forty-seven patients previously diagnosed as having AML or MDS-EB with available mutation analysis data, including targeted next-generation and RNA-sequencing data, were included. We reclassified 15 (31.9%) and 27 (57.4%) patients based on the 2022 WHO and 2022 ICC, respectively. One patient was reclassified as having a translocation categorized as a rare recurring translocation in both classifications. Reclassification was mostly due to the addition of mutation-based diagnostic criteria (i.e., AML, myelodysplasia-related) or a new entity associated with TP53 mutation. In both classifications, MDS diagnosis required the confirmation of multi-hit TP53 alterations. Among 14 patients with TP53 mutations, 11 harbored multi-hit TP53 alterations, including four with TP53 mutations and loss of heterozygosity. Adverse prognosis was associated with multi-hit TP53 alterations (P=0.009) in patients with MDS-EB, emphasizing the importance of detecting the mutations at diagnosis. The implementation of these classifications may lead to the identification of different subtypes from previously heterogeneous diagnostic categories based on genetic characteristics.

National trends in the prevalence of chronic kidney disease among Korean adults, 2007-2020.

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m2, or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007-2010, 5.1% [95% confidence interval (CI) 4.7-5.5]; 2017-2019, 7.1% [95% CI 6.6-7.6]; pandemic period, 6.5% [95% CI 5.7-7.3]; and ßdiff, - 0.19; 95% CI - 0.24 to - 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD.

Performance evaluation and clinical impact of the Oncomine Myeloid Research Assay for gene expression analysis in myeloid haematologic malignancies.

AIM: Gene expression analysis facilitates the detection of diagnostic and prognostic biomarkers for myeloid haematological malignancies. The Oncomine Myeloid Research Assay (OMA; Thermo Fisher Scientific, Massachusetts, USA) provides a comprehensive analysis of gene expression of five target genes, along with gene alteration and fusion. Here, we present the performance of the OMA for gene expression analysis. METHODS: In total, 53 RNA samples from patients diagnosed with acute myeloid leukaemia (AML) or myelodysplastic syndrome were included. Of these 53 samples, 3 were evaluated for reproducibility and 50 were evaluated for comparison with RNA-sequencing (RNA-seq). The prognostic impact of the gene expression profile produced by both OMA and RNA-seq in AML was investigated using follow-up data from 33 patients with AML. RESULTS: The OMA showed good intrarun and interrun reproducibility. Compared with the RNA-seq results, high correlations were found in BAALC, MECOM and WT1 (all r>0.9), with moderate correlations in MYC (r=0.75, p<0.001) and SMC1A (r=0.42, p=0.002). The agreement between OMA and RNA-seq in classifying the dysregulated expression group was almost perfect, except for SMC1A (κ=0.175). Among these five genes, only BAALC showed a significant clinical impact in patients with AML. Patients with high BAALC expression showed significantly shorter overall survival based on both OMA (p=0.037) and RNA-seq (p=0.003). CONCLUSIONS: OMA gene expression analysis offers reproducible and accurate gene expression data for most targeted genes and demonstrates the utility of BAALC expression as a prognostic marker in AML.

COVID-19 vaccine type-dependent differences in immunogenicity and inflammatory response: BNT162b2 and ChAdOx1 nCoV-19.

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1ß levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.

Observational management of Grade II or higher blunt traumatic thoracic aortic injury: 15 years of experience at a single suburban institution.

Background: We aimed to investigate the outcomes after delayed management of ≥ Grade II blunt traumatic thoracic aortic injury (BTAI). Methods: Between January 2005 and December 2019, we retrospectively reviewed the medical records of 21 patients with ≥ Grade II thoracic aortic injury resulting from blunt trauma. Twelve patients underwent observation for the injury, whereas nine patients were transferred immediately after the diagnosis. Patients were divided into a nonoperative management group (n = 7) and delayed repair group (n = 5) based on whether they underwent thoracic endovascular aneurysm repair or surgery. Results: The most common dissection type was DeBakey classification IIIa (n = 9). Five patients underwent delayed surgery (including aneurysm repair), with observation periods ranging from 1 day to 36 months. The delayed repair group exhibited higher injury severity scores than the nonoperative management group (n = 7). The nonoperative management group was followed-up with blood pressure management without a change in status for a period ranging from 3 to 96 months. Conclusions: Our findings indicated that conservative management may be appropriate for select patients with Grade II/III BTAI, especially those exhibiting hemodynamic stability with anti-impulse therapy and minimally sized pseudoaneurysms. However, further studies are required to identify the risk factors for injury progression and long-term outcomes.

Total Platelet Transcriptomics and Its Network Analysis by RNA-Seq and miRNA-Seq and PCA Application in Essential Thrombocythaemia.

Differentiating the aetiology of thrombocytosis is limited yet crucial in patients with essential thrombocythaemia (ET). MicroRNAs (miRNAs) regulate haematopoiesis and lineage commitment; aberrant expression of miRNAs plays an important role in myeloproliferative neoplasms. However, the miRNA profile has been poorly explored in ET patients compared to patients with reactive thrombocytosis (RT). A total of 9 samples, including 5 ET patient samples, 2 RT patient samples, and 2 healthy control samples, were analysed in this study. We produced 81.43 million reads from transcripts and 59.60 million reads from small RNAs. We generated a comprehensive miRNA-mRNA regulatory network and identified unique 14 miRNA expression patterns associated with ET. Among the 14 miRNAs, miR-1268a was downregulated in ET and showed an inverse correlation with its 8 putative target genes, including genes associated with thrombus formation and platelet activation (CDH6, EHD2, FUT1, KIF26A, LINC00346, PTPRN, SERF1A, and SLC6A9). Principal component analysis (PCA) showed ET and non-ET groups well clustered in space, suggesting each group had a distinctive expression pattern of mRNAs and miRNAs. These results suggest that the significant dysregulation of miR-1268a and its 8 target genes could be a unique expression of platelet mi-RNAs and miRNA/mRNA regulatory network in ET patients.

Pembrolizumab-induced severe oral mucositis in a patient with squamous cell carcinoma of the lung: A case study.

BACKGROUND: Immune checkpoint inhibitors, such as pembrolizumab, a humanized monoclonal antibody against programmed death-1, elicit antitumor activity in various types of cancers, including lung cancer. However, pembrolizumab has been reported to cause diverse immune-related adverse events associated with T-cell activation. CASE PRESENTATION: We present the case of a 61-year-old man with advanced non-small cell lung cancer who was administered pembrolizumab as first-line treatment. After the first dose, radiotherapy was also administered because of rapid progression of dyspnea due to bronchial obstruction by the tumor. After the fourth cycle of pembrolizumab treatment, the patient presented with severe oral pain and multiple oral ulcers on the lips and throughout the oral cavity. Diagnostic tests including viral serology, fungal cultures, and esophagogastroscopy did not provide conclusive results. A biopsy of the damaged oral mucosa showed infiltration of inflammatory cells with no other specific findings. In addition, multiple skin rashes were observed on various areas of the patient's body, most notably in the area that had previously been irradiated. Given that there was no other apparent cause, the patient's symptoms were considered to be an immune-related adverse event due to pembrolizumab treatment. The oral mucositis and skin rash gradually improved over a month with corticosteroid treatment. CONCLUSION: Immune checkpoint inhibitors have recently been introduced into the clinical practice. Their use is gradually increasing as monotherapy or in combination with other cytotoxic chemotherapeutic agents. Since immune check point inhibitors such as pembrolizumab have not been used in the clinical setting for very long, we wish to share this case report in order to build a better understating of the rare and unknown side effects of treatment with immune check point inhibitors. The potential side effects of combined therapy must be monitored carefully.

Single-dose etoposide is an effective and safe protocol for stem cell mobilization in patients with multiple myeloma.

BACKGROUND: Single-dose etoposide was used an outpatient-based protocol for mobilization in patients with multiple myeloma (MM) for autologous stem cell transplantation (ASCT). Thus, we retrospectively analyzed the efficacy and safety of our one-day protocol in comparison with that of previous methods. METHODS: We retrospectively analyzed 168 patients with MM who underwent peripheral blood stem cell collection for upfront ASCT between 2008 and 2018. The mobilization protocols included G-CSF alone (G-mobilization), one-day 375 mg/m2 of etoposide (E375), two-days of 375 mg/m2 of etoposide (E750), or one-day high-dose (3.5 g/m2 ) cyclophosphamide (HD CY). For comparison of efficacy of each protocol, collected CD34+ cells over 4 × 106 /kg and under 2 × 106 /kg were defined as "adequate harvest" and "harvest failure," respectively. RESULTS: The median number of collected CD34+ cells was 5.58 × 106 /kg in patients receiving single-dose etoposide, and the percentage of uncomplicated optimal harvest of E375 (65.6%, 21/32) was significantly higher than that of E750 (41.9%, 13/31) and HD CY (31.3%, 15/48). The E375 showed the highest rate of adequate harvest (96.9%, 31/32) compared to that of E750 (87.1%), HD CY (75.0%), and G-mobilization (59.6%). Most E375 patients achieved adequate harvest without complication (29/32, 90.6%), the CD34+ cell collection yield on apheresis days one and two of E375 was not significantly different from that of E750, and no harvest failures occurred for E375. Neutrophil and platelet engraftments were significantly faster in E375 than other groups (P < .001). CONCLUSIONS: The use of single-dose etoposide could be an effective and safe method for mobilization in patients with MM.

Fluorescence-based immunosensor using three-dimensional CNT network structure for sensitive and reproducible detection of oral squamous cell carcinoma biomarker.

A hierarchical three-dimensional network of carbon nanotubes on Si pillar substrate (3DN-CNTs) was developed for the accurate detection of oral squamous cell carcinoma (OSCC) in clinical saliva samples. The 3DN-CNTs were uniformly coated with a layer of aluminum oxides to enhance structural stability during biomarker detection. Cytokeratin-19 antigen (Cyfra 21-1) was utilized as a model biomarker of OSCC for fluorescence-based immunosensor using 3DN-CNTs (3DN-CNTs sensor). The 3DN-CNTs sensor enhances the sensitivity of Cyfra 21-1 detection by increasing the density of immobilized antibody through high surface area of 3DN-CNTs and enhancing the accessibility of biomolecules through the ordered pathway of hierarchical structure. The reliable detection limit for sensing of Cyfra 21-1 was estimated as in the level of 0.5 ng/mL and the quantitative estimation of Cyfra 21-1 was analyzed by 4-parameter logistic (4-PL) model for curve-fitting analysis. Clinical applicability of 3DN-CNTs sensor was evaluated through correlation with the commercially available electrochemiluminescence (ECL) detection system in the hospital. The assay results of the two systems for clinical saliva samples showed a good linear correlation. The 3DN-CNTs sensor offers great potential for accurate diagnosis of OSCC using Cyfra 21-1 biomarker in clinical fluids.

Simultaneous Detection of Dual Prostate Specific Antigens Using Surface-Enhanced Raman Scattering-Based Immunoassay for Accurate Diagnosis of Prostate Cancer.

Accurate analysis of specific biomarkers in clinical serum is essential for early diagnosis and treatment of cancer. Here, a surface-enhanced Raman scattering (SERS)-based immunoassay, using magnetic beads and SERS nano tags, was developed for the determination of free to total (f/t) prostate specific antigen (PSA) ratio to improve the diagnostic performance of prostate cancer. To assess the clinical applicability of the proposed method, SERS-based assays for the simultaneous detection of dual PSA markers, free PSA (f-PSA) and complexed PSA (c-PSA), were performed for clinical samples in the gray zone between 4.0 and 10.0 ng/mL. Our assay results for f/t PSA ratio showed a good linear correlation with those measured using the electrochemiluminescence (ECL) system installed in the clinical laboratory of the University Hospital. In addition, the simultaneous assay provided better precision than parallel assays for the detection of f-PSA and c-PSA in 13 clinical serum samples. Therefore, our SERS-based assay for simultaneous detection of dual PSA markers in clinical fluids has strong potential for application in the accurate diagnosis of prostate cancer.

Comparison between Saliva and Nasopharyngeal Swab Specimens for Detection of Respiratory Viruses by Multiplex Reverse Transcription-PCR.

Nasopharyngeal swabs (NPSs) are being widely used as specimens for multiplex real-time reverse transcription (RT)-PCR for respiratory virus detection. However, it remains unclear whether NPS specimens are optimal for all viruses targeted by multiplex RT-PCR. In addition, the procedure to obtain NPS specimens causes coughing in most patients, which possibly increases the risk of nosocomial spread of viruses. In this study, paired NPS and saliva specimens were collected from 236 adult male patients with suspected acute respiratory illnesses. Specimens were tested for 16 respiratory viruses by multiplex real-time RT-PCR. Among the specimens collected from the 236 patients, at least 1 respiratory virus was detected in 183 NPS specimens (77.5%) and 180 saliva specimens (76.3%). The rates of detection of respiratory viruses were comparable for NPS and saliva specimens (P = 0.766). Nine virus species and 349 viruses were isolated, 256 from NPS specimens and 273 from saliva specimens (P = 0.1574). Adenovirus was detected more frequently in saliva samples (P < 0.0001), whereas influenza virus type A and human rhinovirus were detected more frequently in NPS specimens (P = 0.0001 and P = 0.0289, respectively). The possibility of false-positive adenovirus detection from saliva samples was excluded by direct sequencing. In conclusion, neither of the sampling methods was consistently more sensitive than the other. We suggest that these cost-effective methods for detecting respiratory viruses in mixed NPS-saliva specimens might be valuable for future studies.

MicroRNA-205-5p is upregulated in myelodysplastic syndromes and induces cell proliferation via PTEN suppression.

Micro (mi)RNA dysregulation is implicated in the development of myelodysplastic syndrome (MDS). Chromosomal abnormalities on 1q are frequently detected in Korean patients with MDS; however, how these are related to disease development is unknown. The present study compared the expression profiles of miRNAs encoded by chromosome 1q between 65 MDS patients and 11 controls. We found that miR-205-5p levels were 12.5 fold higher in the former (P=0.001). miR-205-5p level was increased in 44.7% of patients when an arbitrary 2(-ΔCt) cut-off value of 1.25 was used. miR-205-5p expression data were used to generate a receiver operating characteristic (ROC) curve for miR-205-5p, for which the area under the curve (AUC) was 0.825 (95% confidence interval: 0.710-0.941; P=0.001). Moreover, transfection with a miR-205-5p mimic induced cell proliferation by inhibiting the expression of the tumor suppressor protein phosphatase and tensin homolog (PTEN). Our findings suggest that miR-205-5p upregulation contributes to MDS by suppressing PTEN and that miR-205-5p thus acts as an oncogene in hematopoietic cells.

Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells.

BACKGROUND/AIMS: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. METHODS: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. RESULTS: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-κB (NF-κB) and ß-catenin. CONCLUSIONS: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-κB and ß-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.

MicroRNA-194-5p could serve as a diagnostic and prognostic biomarker in myelodysplastic syndromes.

Trisomy 8 and trisomy 1q are the most frequent chromosomal abnormalities in Korean patients with myelodysplastic syndrome (MDS). MicroRNA (miRNA) deregulation is involved in the development of hematological malignancies, including MDS, and cancer-associated genomic regions are known to encode miRNAs. The aim of the present study was to investigate the involvement of miRNAs encoded by chromosomes 8 and 1q in MDS. For this, the expression of nine miRNAs encoded by chromosome 8 (miR-30b-5p, miR-30d-5p, miR-101-3p, miR-124-3p, miR-151a-5p, miR-320a, miR-486-5p, miR-596, and miR-875-5p) and three miRNAs encoded by chromosome 1q (miR-29c-3p, miR-194-5p, and miR-214-3p) was compared between 65 MDS patients and 11 controls. We found a significant upregulation of miR-194-5p (5.1-fold, P=0.002) and miR-320a (2.94-fold, P=0.016) in MDS patients compared with controls. The patients with low miR-194-5p expression showed a significantly decreased overall survival (P=0.049). The areas under the miR-194-5p and miR-320a ROC curves were 0.797 (P=0.002) and 0.729 (P=0.016), respectively. Although these findings need to be validated in a larger patient population, our results indicate that miR-194-5p is a candidate diagnostic biomarker for MDS and that low miR-194-5p expression could be associated with poor overall survival for MDS patients.

A case report of a fetus with mosaic autosomal variegated aneuploidies and literature review.

Mosaic variegated aneuploidy (MVA) is a recessive condition characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple chromosomes and tissues. The phenotype of MVA syndrome includes severe microcephaly and growth deficiency, central nervous system anomalies, mental retardation, mild physical anomalies, and predisposition to cancer. We report a case of true fetal mosaicism for variegated aneuploidies detected in amniotic fluid cells. A 33-year-old primigravida woman at 5 weeks 1 day of gestation was referred to our tertiary hospital because of a high-risk pregnancy associated with IgA nephropathy. In a quadruple screening test performed at the 15(th) week of gestation, alpha fetoprotein was 73.4 IU/mL (2.792 MoM), suggesting that she was at high risk of neural tube defect. Following amniocentesis performed at the 17 weeks' gestation, chromosome examination of amniocyte culture showed premature chromatic separation in 63% of the metaphases (58/92) and a high frequency of gain and loss of chromosomes. Repeat amniocentesis at 21 weeks' gestation consistently showed the presence of multiple mosaic autosomal variegated aneuploidies. Ultrasonography at 21 weeks' gestation revealed relatively small head circumference for gestational age (<3%) and vermis defect, suggesting that the fetus would have microcephaly and Dandy-Walker malformation. Cytogenetic analysis with peripheral blood of the parents showed normal karyotype. In summary, we hereby report the cytogenetic analysis and prenatal findings of MVA.