Pub Date : 2025-11-01Epub Date: 2025-09-03DOI: 10.3343/alm.2025.0010
Jong Do Seo, Gye Cheol Kwon, Jeong-Ho Kim, Sang-Guk Lee, Junghan Song, Pil-Whan Park, Dongheui An, Qute Choi, Chan-Ik Cho, Sollip Kim, Yeo-Min Yun
Background: Ensuring reference material (RM) commutability is crucial for evaluating measurement traceability in order to standardize laboratory tests. However, commutability assessment is not routinely performed. We assessed whether RMs prepared following CLSI C37-A guidelines could be used without assessing commutability by evaluating their commutability for four lipid measurements using the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and CLSI EP14 protocols.
Methods: We analyzed total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in frozen sera from 20 individuals and 11 RMs, prepared by the Korea Disease Control and Prevention Agency-Laboratory Standardization Project (per CLSI C37-A), using six routine measurement procedures (MPs). Regression equations and 95% prediction intervals derived from single-donor sera were analyzed following CLSI EP14. The IFCC protocol was used to assess differences in inter-MP biases between RM and clinical samples. The effect of the TG concentration on commutability was evaluated by analyzing biases between MP results and reference procedure-assigned values.
Results: RMs were commutable for most MP pairs for TC and TG. Commutability for HDL-C and LDL-C varied across RMs, with RM10 and RM11 showing higher TG levels (2.38 and 2.95 mmol/L, respectively) and lower commutability. Increased bias percentages from assigned values were observed for RMs with higher TG levels.
Conclusions: RMs prepared per CLSI C37-A were commutable with most MP pairs for TC and TG. Elevated TG levels affected HDL-C and LDL-C commutability, highlighting the need to consider TG concentrations during RM preparation and assess commutability to standardize laboratory tests.
{"title":"Can Reference Materials Prepared Following CLSI C37-A Be Utilized Without Commutability Assessment? Perspectives Based on Lipid Measurements.","authors":"Jong Do Seo, Gye Cheol Kwon, Jeong-Ho Kim, Sang-Guk Lee, Junghan Song, Pil-Whan Park, Dongheui An, Qute Choi, Chan-Ik Cho, Sollip Kim, Yeo-Min Yun","doi":"10.3343/alm.2025.0010","DOIUrl":"10.3343/alm.2025.0010","url":null,"abstract":"<p><strong>Background: </strong>Ensuring reference material (RM) commutability is crucial for evaluating measurement traceability in order to standardize laboratory tests. However, commutability assessment is not routinely performed. We assessed whether RMs prepared following CLSI C37-A guidelines could be used without assessing commutability by evaluating their commutability for four lipid measurements using the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and CLSI EP14 protocols.</p><p><strong>Methods: </strong>We analyzed total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in frozen sera from 20 individuals and 11 RMs, prepared by the Korea Disease Control and Prevention Agency-Laboratory Standardization Project (per CLSI C37-A), using six routine measurement procedures (MPs). Regression equations and 95% prediction intervals derived from single-donor sera were analyzed following CLSI EP14. The IFCC protocol was used to assess differences in inter-MP biases between RM and clinical samples. The effect of the TG concentration on commutability was evaluated by analyzing biases between MP results and reference procedure-assigned values.</p><p><strong>Results: </strong>RMs were commutable for most MP pairs for TC and TG. Commutability for HDL-C and LDL-C varied across RMs, with RM10 and RM11 showing higher TG levels (2.38 and 2.95 mmol/L, respectively) and lower commutability. Increased bias percentages from assigned values were observed for RMs with higher TG levels.</p><p><strong>Conclusions: </strong>RMs prepared per CLSI C37-A were commutable with most MP pairs for TC and TG. Elevated TG levels affected HDL-C and LDL-C commutability, highlighting the need to consider TG concentrations during RM preparation and assess commutability to standardize laboratory tests.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"562-573"},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-26DOI: 10.3343/alm.2025.0314
{"title":"Erratum: Comparing Genomic Characteristics of <i>Streptococcus pyogenes</i> Associated with Invasiveness over a 20-year Period in Korea.","authors":"","doi":"10.3343/alm.2025.0314","DOIUrl":"10.3343/alm.2025.0314","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"638"},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-03-21DOI: 10.3343/alm.2024.0555
Marco Amato, Lisa Seekircher, Lena Tschiderer, Peter Willeit, Harald Schennach, Anita Siller
Background: Pooled platelet (PLT) production methods differ worldwide. In Europe, the buffy coat (BC) method is predominantly used, with four to eight BCs being pooled to produce single- or double-dose PLT products. The European Directorate for the Quality of Medicines & HealthCare (EDQM) blood guide and Austrian legislation define a therapeutic PLT unit as ≥ 2 × 1011 PLTs/unit. We optimized the manufacturing steps to produce double-dose PLT products from six BCs, aiming to enhance production efficiency while maintaining product quality.
Methods: We stepwise optimized our protocol starting from five BCs (BC5) (N=107). First, we included an additional BC (BC6) (N=110). Second, we used a hematology analyzer (Sysmex XN-1000) equipped with blood bank mode, which is a novel software application for measuring PLT counts in PLT units (BC6+XN-1000) (N=106). Third, we optimized the blood cell separator (BCS) settings to produce higher-volume BCs (BC6+XN-1000+BCS) (N=107). Fourth, we adapted the centrifugation (BC6+XN-1000+BCS+CF) (N=197). All units were pathogen-inactivated using the INTERCEPT blood system (amotosalen/ultraviolet A).
Results: Each optimization step significantly increased the yield ( × 1011/PLT concentrate) (P <0.001). The mean yield increased from 2.83 (SD 0.39) for BC5 to 4.81 (SD 0.58) for BC6+XN-1000+BCS+CF. The mean BC volume increased from 47.78 mL (SD 5.09) to 55.59 mL (SD 5.11) following BCS adaptions (P <0.001).
Conclusions: After stepwise protocol optimization, we could produce pathogen-inactivated double-dose PLT concentrates by pooling six BCs, complying with national regulations and EDQM quality requirements while reducing costs and minimizing blood wastage.
{"title":"Optimized Protocol for Producing Pathogen-inactivated Double-dose Platelet Concentrates From Six Pooled Buffy Coats.","authors":"Marco Amato, Lisa Seekircher, Lena Tschiderer, Peter Willeit, Harald Schennach, Anita Siller","doi":"10.3343/alm.2024.0555","DOIUrl":"10.3343/alm.2024.0555","url":null,"abstract":"<p><strong>Background: </strong>Pooled platelet (PLT) production methods differ worldwide. In Europe, the buffy coat (BC) method is predominantly used, with four to eight BCs being pooled to produce single- or double-dose PLT products. The European Directorate for the Quality of Medicines & HealthCare (EDQM) blood guide and Austrian legislation define a therapeutic PLT unit as ≥ 2 × 10<sup>11</sup> PLTs/unit. We optimized the manufacturing steps to produce double-dose PLT products from six BCs, aiming to enhance production efficiency while maintaining product quality.</p><p><strong>Methods: </strong>We stepwise optimized our protocol starting from five BCs (BC5) (N=107). First, we included an additional BC (BC6) (N=110). Second, we used a hematology analyzer (Sysmex XN-1000) equipped with blood bank mode, which is a novel software application for measuring PLT counts in PLT units (BC6+XN-1000) (N=106). Third, we optimized the blood cell separator (BCS) settings to produce higher-volume BCs (BC6+XN-1000+BCS) (N=107). Fourth, we adapted the centrifugation (BC6+XN-1000+BCS+CF) (N=197). All units were pathogen-inactivated using the INTERCEPT blood system (amotosalen/ultraviolet A).</p><p><strong>Results: </strong>Each optimization step significantly increased the yield ( × 10<sup>11</sup>/PLT concentrate) (<i>P</i> <0.001). The mean yield increased from 2.83 (SD 0.39) for BC5 to 4.81 (SD 0.58) for BC6+XN-1000+BCS+CF. The mean BC volume increased from 47.78 mL (SD 5.09) to 55.59 mL (SD 5.11) following BCS adaptions (<i>P</i> <0.001).</p><p><strong>Conclusions: </strong>After stepwise protocol optimization, we could produce pathogen-inactivated double-dose PLT concentrates by pooling six BCs, complying with national regulations and EDQM quality requirements while reducing costs and minimizing blood wastage.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"601-608"},"PeriodicalIF":3.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundAlpha-fetoprotein (AFP) and its isoform AFP-L3 are well-established serum biomarkers for hepatocellular carcinoma (HCC), a common malignancy and a leading cause of cancer-related mortality worldwide. Current methods for measuring these biomarkers are primarily lectin-based assays including the liquid-phase binding assay (LiBA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), both of which have limitations in diagnostic sensitivity and clinical utility for samples with low AFP concentrations. We aimed to develop a lectin-independent LC-MS/MS method for quantifying fucosylated AFP proteins (AFP-Fuc%).MethodsWe conducted analytical validation, including method comparisons, over 2 months. The analytical sensitivity and diagnostic performance of this method were evaluated using 525 human serum samples-235 from HCC patients and 290 from non-HCC individuals-and compared with those of LiBA, which measured AFP-L3 levels.ResultsThe LC-MS/MS method demonstrated acceptable within-laboratory imprecision (CVs<17.1%) without detectable bias, carryover, or matrix effects. Our method exhibited a broader linear dynamic range (spanning five orders of magnitude) and 10-fold higher analytical sensitivity than LiBA. The diagnostic performance of our method was significantly superior to that of LiBA, particularly in patients with low AFP concentrations (<7 ng/mL, P <0.001), with improved accuracy, sensitivity, and precision at a specificity of 96.2%.ConclusionsThe validated LC-MS/MS method demonstrated robust analytical performance and superior diagnostic accuracy over LiBA for HCC diagnosis while avoiding the inherent limitations of lectin-based assays. Our LC-MS/MS assay shows promise for early HCC detection and may contribute to enhanced patient care.
甲胎蛋白（AFP）及其异构体AFP- l3是公认的肝细胞癌（HCC）血清生物标志物，HCC是一种常见的恶性肿瘤，也是全球癌症相关死亡的主要原因。目前测量这些生物标志物的方法主要是基于凝集素的分析，包括液相结合分析（LiBA）和液相色谱-串联质谱分析（LC-MS/MS），这两种方法在诊断敏感性和临床应用方面都有局限性，用于低AFP浓度的样品。我们的目的是建立一种不依赖凝集素的LC-MS/MS方法来定量浓缩AFP蛋白（AFP- fuc %）。方法进行为期2个月的分析验证，包括方法比较。使用525份人血清样本（235份来自HCC患者，290份来自非HCC患者）对该方法的分析敏感性和诊断性能进行了评估，并与LiBA测定的AFP-L3水平进行了比较。结果LC-MS/MS方法具有可接受的实验室内不精密度（CVs<17.1%），没有可检测到的偏倚、携带或基质效应。我们的方法具有更宽的线性动态范围（跨越5个数量级）和比LiBA高10倍的分析灵敏度。本方法的诊断性能明显优于LiBA，特别是在AFP浓度较低（<7 ng/mL, P <0.001）的患者中，准确度、灵敏度和精密度均有提高，特异性为96.2%。结论经验证的LC-MS/MS方法在HCC诊断中表现出强大的分析性能和更高的诊断准确性，同时避免了基于凝集素的检测的固有局限性。我们的LC-MS/MS分析显示了早期HCC检测的希望，并可能有助于加强患者护理。
{"title":"Development and Validation of a Lectin-independent Liquid Chromatography-Tandem Mass Spectrometry Method for Serum Glycosylated Alpha-fetoprotein Analysis and Comparison with a Liquid-phase Binding Assay.","authors":"Hyojin Kim,Juri Park,Hanseul Suh,Saeyoung Lee,Yoonha Park,Won Suk Yang,Dohsik Minn,Soon Sun Kim,Jae Youn Cheong,Je-Hyun Baek","doi":"10.3343/alm.2025.0003","DOIUrl":"https://doi.org/10.3343/alm.2025.0003","url":null,"abstract":"BackgroundAlpha-fetoprotein (AFP) and its isoform AFP-L3 are well-established serum biomarkers for hepatocellular carcinoma (HCC), a common malignancy and a leading cause of cancer-related mortality worldwide. Current methods for measuring these biomarkers are primarily lectin-based assays including the liquid-phase binding assay (LiBA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), both of which have limitations in diagnostic sensitivity and clinical utility for samples with low AFP concentrations. We aimed to develop a lectin-independent LC-MS/MS method for quantifying fucosylated AFP proteins (AFP-Fuc%).MethodsWe conducted analytical validation, including method comparisons, over 2 months. The analytical sensitivity and diagnostic performance of this method were evaluated using 525 human serum samples-235 from HCC patients and 290 from non-HCC individuals-and compared with those of LiBA, which measured AFP-L3 levels.ResultsThe LC-MS/MS method demonstrated acceptable within-laboratory imprecision (CVs<17.1%) without detectable bias, carryover, or matrix effects. Our method exhibited a broader linear dynamic range (spanning five orders of magnitude) and 10-fold higher analytical sensitivity than LiBA. The diagnostic performance of our method was significantly superior to that of LiBA, particularly in patients with low AFP concentrations (<7 ng/mL, P <0.001), with improved accuracy, sensitivity, and precision at a specificity of 96.2%.ConclusionsThe validated LC-MS/MS method demonstrated robust analytical performance and superior diagnostic accuracy over LiBA for HCC diagnosis while avoiding the inherent limitations of lectin-based assays. Our LC-MS/MS assay shows promise for early HCC detection and may contribute to enhanced patient care.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min-Seung Park,Jae Joon Lee,Darae Kim,Jin-Oh Choi,Seok Jin Kim,Kihyun Kim,Ju-Hong Min,Hyun-Young Kim,Hee-Jin Kim
BackgroundTransthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv.MethodsWe retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives.ResultsPathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant.ConclusionsThis study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.
{"title":"Unique TTR Variants D38A and M13dup Among Korean Patients with Hereditary Transthyretin Amyloidosis: A Retrospective Single-Center Cohort Study.","authors":"Min-Seung Park,Jae Joon Lee,Darae Kim,Jin-Oh Choi,Seok Jin Kim,Kihyun Kim,Ju-Hong Min,Hyun-Young Kim,Hee-Jin Kim","doi":"10.3343/alm.2025.0236","DOIUrl":"https://doi.org/10.3343/alm.2025.0236","url":null,"abstract":"BackgroundTransthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv.MethodsWe retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives.ResultsPathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant.ConclusionsThis study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"57 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundBlastic plasmacytoid dendritic cell neoplasms (BPDCNs) are rare and aggressive hematologic malignancies with poorly defined molecular characteristics. Genetic data for Korean patients with this condition are scarce. We conducted the first network-based analysis of Korean patients with BPDCN, using next-generation sequencing (NGS) alongside clinical, morphological, and cytogenetic evaluations.MethodsWe included 14 patients diagnosed with BPDCN between 2004 and 2021. Clinical, morphological, and cytogenetic data were collected. Conventional karyotyping and targeted NGS were performed. Network analysis was used to link gene variants with known BPDCN-associated genes.ResultsThe median age at diagnosis was 52 yrs; the male:female ratio was 1.8:1. Cutaneous and bone marrow (BM) involvement were observed in 79% and 57% of patients at diagnosis, respectively; 85% of those not lost to follow-up eventually showed BM involvement. Allogeneic hematopoietic stem cell transplantation was associated with longer survival compared with chemotherapy alone (P=0.015). Complex karyotypes were common (87%), with novel chromosomal deletions at 1p, 18q, and 22q. BPDCN samples showed recurrent variations in TET2, ASXL1, and RAS-pathway genes, as well as novel variations in 22 genes, including SMARCD2, DDX3X, and GNB1. Network analysis revealed functional associations between these novel alterations and established BPDCN-related genes.ConclusionsWe present the first network-based analysis of Korean patients with BPDCN, along with conventional genetic assessments, highlighting the potential genetic drivers of BPDCN and facilitating the development of targeted therapies for the disease.
{"title":"Clinico-hematopathologic and Genetic Characteristics of Korean Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Single-center Cohort Study.","authors":"Jiyeon Kim,Miyoung Kim,Daehyun Chu,Young-Uk Cho,Sang-Hyun Hwang,Seongsoo Jang,Eul-Ju Seo,Eun-Ji Choi,Han-Seung Park,Jung-Hee Lee,Je-Hwan Lee,Dok Hyun Yoon,Heounjeong Go,Chan Sik Park,Kyoo-Hyung Lee,Chan-Jeoung Park,Seungwoo Hwang","doi":"10.3343/alm.2025.0395","DOIUrl":"https://doi.org/10.3343/alm.2025.0395","url":null,"abstract":"BackgroundBlastic plasmacytoid dendritic cell neoplasms (BPDCNs) are rare and aggressive hematologic malignancies with poorly defined molecular characteristics. Genetic data for Korean patients with this condition are scarce. We conducted the first network-based analysis of Korean patients with BPDCN, using next-generation sequencing (NGS) alongside clinical, morphological, and cytogenetic evaluations.MethodsWe included 14 patients diagnosed with BPDCN between 2004 and 2021. Clinical, morphological, and cytogenetic data were collected. Conventional karyotyping and targeted NGS were performed. Network analysis was used to link gene variants with known BPDCN-associated genes.ResultsThe median age at diagnosis was 52 yrs; the male:female ratio was 1.8:1. Cutaneous and bone marrow (BM) involvement were observed in 79% and 57% of patients at diagnosis, respectively; 85% of those not lost to follow-up eventually showed BM involvement. Allogeneic hematopoietic stem cell transplantation was associated with longer survival compared with chemotherapy alone (P=0.015). Complex karyotypes were common (87%), with novel chromosomal deletions at 1p, 18q, and 22q. BPDCN samples showed recurrent variations in TET2, ASXL1, and RAS-pathway genes, as well as novel variations in 22 genes, including SMARCD2, DDX3X, and GNB1. Network analysis revealed functional associations between these novel alterations and established BPDCN-related genes.ConclusionsWe present the first network-based analysis of Korean patients with BPDCN, along with conventional genetic assessments, highlighting the potential genetic drivers of BPDCN and facilitating the development of targeted therapies for the disease.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"92 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyun-Young Kim,Boram Kim,Min-Seung Park,Jong-Ho Park,Hee Young Ju,Keon Hee Yoo,Jun Ho Jang,Chul Won Jung,Hee-Jin Kim
BackgroundFusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNA-seq) compared with that of conventional diagnostics in patients with acute leukemia.MethodsWe retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics.ResultsRNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel (KMT2A::THAP12, RUNX1::PRPF19, MLLT10::UBE2L6, and FUS::ZNF362) and three rare (HNRNPH1::ERG, RUNX1::USP42, and ETV6::NCOA2) fusions.ConclusionsThis was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.
融合基因是急性白血病的主要驱动因素。常规诊断在检测不同的融合包括在最近更新的急性白血病分类是有限的。我们评估了RNA测序（RNA-seq）与常规诊断方法在急性白血病患者中的融合检测性能。方法回顾性分析2022年9月至2023年9月在韩国首尔三星医疗中心进行常规诊断（即核型、FISH或多重反转录PCR）的101例急性白血病患者的资料。全rna测序使用Illumina搁浅mRNA Prep试剂盒（Illumina, San Diego， CA， USA）。将RNA-seq检测融合基因的一致性、敏感性和特异性与常规诊断方法进行比较。结果101例急性髓系白血病、b细胞急性淋巴母细胞白血病、t细胞急性淋巴母细胞白血病和混合表型急性白血病中，51例（50.5%）的rna -seq共鉴定出52个融合基因，检出率分别为40.7%、70.3%、37.5%和50%。RNA-seq的敏感性为83.3%，与常规诊断的一致性为80.8%；它错过了8个融合，可能是因为转录物丰度低或增强子劫持。RNA-seq还帮助澄清了以前未明确的三种重排，并在56例常规诊断阴性的病例中检测到12种融合（21.4%），包括4种新型融合（KMT2A::THAP12、RUNX1::PRPF19、MLLT10::UBE2L6和FUS::ZNF362）和3种罕见融合（HNRNPH1::ERG、RUNX1::USP42和ETV6::NCOA2）。结论：这是韩国首次评估全RNA-seq在急性白血病患者融合检测中的表现。将RNA-seq纳入诊断工作流程可能有助于更早和更精确的治疗决策，并改善急性白血病患者的预后评估。
{"title":"Detection of Fusion Genes Using RNA Sequencing in Acute Leukemia.","authors":"Hyun-Young Kim,Boram Kim,Min-Seung Park,Jong-Ho Park,Hee Young Ju,Keon Hee Yoo,Jun Ho Jang,Chul Won Jung,Hee-Jin Kim","doi":"10.3343/alm.2025.0300","DOIUrl":"https://doi.org/10.3343/alm.2025.0300","url":null,"abstract":"BackgroundFusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNA-seq) compared with that of conventional diagnostics in patients with acute leukemia.MethodsWe retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics.ResultsRNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel (KMT2A::THAP12, RUNX1::PRPF19, MLLT10::UBE2L6, and FUS::ZNF362) and three rare (HNRNPH1::ERG, RUNX1::USP42, and ETV6::NCOA2) fusions.ConclusionsThis was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jong-Sung Park,Kyung Hee Lim,Dae-Hyun Kim,Kwang-Min Lee,Kwang-Sook Woo,Jin-Yeong Han
BackgroundCurrent guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF). However, their plasma concentrations in Korean patients are not well understood.MethodsWe conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays.ResultsWe selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N=252), edoxaban (N=182), or rivaroxaban (N=25). The 5th-95th percentile ranges of the peak concentrations were 84-414 ng/mL (apixaban), 72-424 ng/mL (edoxaban), and 97-517 ng/mL (rivaroxaban). The respective 5th-95th percentile ranges of the trough concentrations were 44-237 ng/mL, 23-93 ng/mL, and 13-219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges.ConclusionsA considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.
{"title":"Peak and Trough Concentration Ranges of Factor Xa Inhibitors for Preventing Thromboembolic Stroke in Korean Patients with Non-valvular Atrial Fibrillation.","authors":"Jong-Sung Park,Kyung Hee Lim,Dae-Hyun Kim,Kwang-Min Lee,Kwang-Sook Woo,Jin-Yeong Han","doi":"10.3343/alm.2025.0144","DOIUrl":"https://doi.org/10.3343/alm.2025.0144","url":null,"abstract":"BackgroundCurrent guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF). However, their plasma concentrations in Korean patients are not well understood.MethodsWe conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays.ResultsWe selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N=252), edoxaban (N=182), or rivaroxaban (N=25). The 5th-95th percentile ranges of the peak concentrations were 84-414 ng/mL (apixaban), 72-424 ng/mL (edoxaban), and 97-517 ng/mL (rivaroxaban). The respective 5th-95th percentile ranges of the trough concentrations were 44-237 ng/mL, 23-93 ng/mL, and 13-219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges.ConclusionsA considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"102 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joung Ha Park,Hyemin Chung,Min-Chul Kim,Seong-Ho Choi,Jin-Won Chung,Hye Ryoun Kim
BackgroundDespite widespread vaccination efforts against severe acute respiratory syndrome coronavirus 2, variants with increased transmissibility or immune evasion continue to emerge, posing a considerable challenge. Understanding the immunological factors associated with coronavirus disease (COVID-19) progression is essential for improving patient management and treatment strategies. We explored the dynamic changes in the peripheral white blood cell (WBC) profile, including T lymphocyte subsets, to assess their potential as predictors of disease severity and progression.MethodsTwo hundred fifty-eight patients hospitalized for confirmed COVID-19 were classified into four sub-cohorts based on changes in disease severity over 7 days. WBC parameters, including absolute neutrophil, total lymphocyte, and T cell subset counts, and the neutrophil-to-lymphocyte ratio (NLR) were assessed at admission and after 7 days.ResultsPatients with persistent mild-to-moderate illness exhibited a marked increase in the lymphocyte count and a decrease in the NLR over time. In contrast, patients with sustained severe-to-critical illness showed an increasing WBC count without a corresponding increase in the lymphocyte count, in addition to a marked elevation in the NLR. Patients whose condition improved from severe-to-critical to mild-to-moderate illness showed increased cluster of differentiation (CD)3+ and CD4+ T cell counts and an elevated CD4/CD8 ratio, whereas the NLR did not significantly change.ConclusionsThe early-phase dynamics of T cell subsets may serve as a useful biomarker of disease severity and recovery in patients with COVID-19. Monitoring these immunological changes may help support clinical decision-making and inform the timing of therapeutic interventions.
{"title":"Peripheral White Blood Cell Dynamics as a Biomarker of Coronavirus Disease Severity.","authors":"Joung Ha Park,Hyemin Chung,Min-Chul Kim,Seong-Ho Choi,Jin-Won Chung,Hye Ryoun Kim","doi":"10.3343/alm.2025.0209","DOIUrl":"https://doi.org/10.3343/alm.2025.0209","url":null,"abstract":"BackgroundDespite widespread vaccination efforts against severe acute respiratory syndrome coronavirus 2, variants with increased transmissibility or immune evasion continue to emerge, posing a considerable challenge. Understanding the immunological factors associated with coronavirus disease (COVID-19) progression is essential for improving patient management and treatment strategies. We explored the dynamic changes in the peripheral white blood cell (WBC) profile, including T lymphocyte subsets, to assess their potential as predictors of disease severity and progression.MethodsTwo hundred fifty-eight patients hospitalized for confirmed COVID-19 were classified into four sub-cohorts based on changes in disease severity over 7 days. WBC parameters, including absolute neutrophil, total lymphocyte, and T cell subset counts, and the neutrophil-to-lymphocyte ratio (NLR) were assessed at admission and after 7 days.ResultsPatients with persistent mild-to-moderate illness exhibited a marked increase in the lymphocyte count and a decrease in the NLR over time. In contrast, patients with sustained severe-to-critical illness showed an increasing WBC count without a corresponding increase in the lymphocyte count, in addition to a marked elevation in the NLR. Patients whose condition improved from severe-to-critical to mild-to-moderate illness showed increased cluster of differentiation (CD)3+ and CD4+ T cell counts and an elevated CD4/CD8 ratio, whereas the NLR did not significantly change.ConclusionsThe early-phase dynamics of T cell subsets may serve as a useful biomarker of disease severity and recovery in patients with COVID-19. Monitoring these immunological changes may help support clinical decision-making and inform the timing of therapeutic interventions.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Sang Yoon,Joo An Kwon,Jeong Seob Shin,Hyun Soo Seok,In Young Yoo,Yeon-Joon Park
BackgroundRapid pathogen identification and antibiotic-susceptibility tests (ASTs) are important for treating bloodstream infections. We compared the performance of the QMAC-dRAST and BD Phoenix M50 direct AST (dPhoenix) systems using bacterial pellets prepared from positive blood culture broth and evaluated their impact on treatment modification.MethodsDirect AST results for 106 Enterobacterales isolates were retrospectively reviewed. Conventional broth microdilution was used to calculate categorical agreement (CA), very major error (VME), major error (ME), and minor error (mE). For isolates showing high VMEs in both methods, supplementary tests were performed. Clinical impact was evaluated by calculating the time required to obtain AST results (time-to-result) and observing changes in antibiotics prescribed after performing ASTs.ResultsBoth systems showed acceptable overall CA, VME, ME, and mE values (QMAC-dRAST: 93.6%, 1.6%, 0.9%, and 5.3%, respectively; dPhoenix: 93.1%, 0.9%, 0.6%, and 6.2%, respectively). Piperacillin-tazobactam showed high VMEs with QMAC-dRAST (4/20, 20.0%) and dPhoenix (3/20, 15.0%). Colony AST on 13 isolates revealed that QMAC-dRAST testing yielded lower minimal inhibitory concentrations (MICs) for piperacillin-tazobactam with three isolates, whereas dPhoenix testing yielded higher MICs with two isolates and lower MICs with two isolates. The average time-to-result was 20.8 hr and 30.1 hr for QMAC-dRAST and dPhoenix, respectively (P <0.001). After AST, the number of optimal treatments increased from 43 (46.7%) to 72 (78.3%) (P <0.001).ConclusionsThe QMAC-dRAST and dPhoenix systems provided reliable AST results with a short time-to-result. However, we recommend performing complementary tests, such as the disk diffusion test, for piperacillin-tazobactam.
{"title":"Accuracy of Two Direct Antibiotic-susceptibility Tests and Their Impact on the Optimal Treatment of Enterobacterales-associated Bloodstream Infection: Comparison of the QMAC-dRAST V2.5 and BD Phoenix M50 Systems.","authors":"Ji Sang Yoon,Joo An Kwon,Jeong Seob Shin,Hyun Soo Seok,In Young Yoo,Yeon-Joon Park","doi":"10.3343/alm.2025.0246","DOIUrl":"https://doi.org/10.3343/alm.2025.0246","url":null,"abstract":"BackgroundRapid pathogen identification and antibiotic-susceptibility tests (ASTs) are important for treating bloodstream infections. We compared the performance of the QMAC-dRAST and BD Phoenix M50 direct AST (dPhoenix) systems using bacterial pellets prepared from positive blood culture broth and evaluated their impact on treatment modification.MethodsDirect AST results for 106 Enterobacterales isolates were retrospectively reviewed. Conventional broth microdilution was used to calculate categorical agreement (CA), very major error (VME), major error (ME), and minor error (mE). For isolates showing high VMEs in both methods, supplementary tests were performed. Clinical impact was evaluated by calculating the time required to obtain AST results (time-to-result) and observing changes in antibiotics prescribed after performing ASTs.ResultsBoth systems showed acceptable overall CA, VME, ME, and mE values (QMAC-dRAST: 93.6%, 1.6%, 0.9%, and 5.3%, respectively; dPhoenix: 93.1%, 0.9%, 0.6%, and 6.2%, respectively). Piperacillin-tazobactam showed high VMEs with QMAC-dRAST (4/20, 20.0%) and dPhoenix (3/20, 15.0%). Colony AST on 13 isolates revealed that QMAC-dRAST testing yielded lower minimal inhibitory concentrations (MICs) for piperacillin-tazobactam with three isolates, whereas dPhoenix testing yielded higher MICs with two isolates and lower MICs with two isolates. The average time-to-result was 20.8 hr and 30.1 hr for QMAC-dRAST and dPhoenix, respectively (P <0.001). After AST, the number of optimal treatments increased from 43 (46.7%) to 72 (78.3%) (P <0.001).ConclusionsThe QMAC-dRAST and dPhoenix systems provided reliable AST results with a short time-to-result. However, we recommend performing complementary tests, such as the disk diffusion test, for piperacillin-tazobactam.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"79 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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