Current Issue

  • Review Article2024-07-01

    Guide to Rho(D) Immune Globulin in Women With Molecularly Defined Asian-type DEL (c.1227G>A)

    In Hwa Jeong , M.D., SooHo Yu , M.D., Tae Yeul Kim , M.D., Soo-Young Oh , M.D., and Duck Cho , M.D.

    Ann Lab Med 2024; 44(4): 307-313

    Abstract : Rh hemolytic disease of the fetus and newborn is a potential risk for D-negative mothers who produce anti-D during pregnancy, which can lead to morbidity and mortality in subsequent pregnancies. To prevent this hemolytic disease, Rho(D) immune globulin (RhIG) is generally administered to D-negative mothers without anti-D at 28 weeks of gestation and shortly after delivery. However, current guidelines suggest that pregnant mothers with molecularly defined weak D types 1, 2, 3, 4.0, and 4.1 do not need RhIG as they are unlikely to produce alloanti-D when exposed to fetuses with D-positive red cells. This issue and the necessity of RHD genotyping have been extensively discussed in Western countries, where these variants are relatively common. Recent evidence indicates that women with Asian-type DEL (c.1227G>A) also do not form alloanti-D when exposed to D-positive red cells. We report that mothers with molecularly defined Asian-type DEL, similar to those with weak D types 1, 2, 3, 4.0, and 4.1, do not require RhIG before and after delivery. Collectively, this review could pave the way for the revision of international guidelines to include the selective use of RhIG based on specific genotypes, particularly in women with the Asian-type DEL.

  • Review Article2024-07-01

    Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation

    Na Kyung Lee , Ph.D. and Jong Wook Chang , Ph.D.

    Ann Lab Med 2024; 44(4): 314-323

    Abstract : The safety and efficacy of both cell and gene therapies have been demonstrated in numerous preclinical and clinical trials. Chimeric antigen receptor T (CAR-T) cell therapy, which leverages the technologies of both cell and gene therapies, has also shown great promise for treating various cancers. Advancements in pertinent fields have also highlighted challenges faced while manufacturing cell and gene therapy products. Potential problems and obstacles must be addressed to ease the clinical translation of individual therapies. Literature reviews of representative cell-based, gene-based, and cell-based gene therapies with regard to their general manufacturing processes, the challenges faced during manufacturing, and QC specifications are limited. We review the general manufacturing processes of cell and gene therapies, including those involving mesenchymal stem cells, viral vectors, and CAR-T cells. The complexities associated with the manufacturing processes and subsequent QC/validation processes may present challenges that could impede the clinical progression of the products. This article addresses these potential challenges. Further, we discuss the use of the manufacturing model and its impact on cell and gene therapy.

  • Original Article2024-07-01 Diagnostic Hematology

    Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies

    Yeeun Shim , M.S., Yu-Kyung Koo , M.D., Saeam Shin , M.D., Ph.D., Seung-Tae Lee , M.D., Ph.D., Kyung-A Lee , M.D., Ph.D., and Jong Rak Choi , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 324-334

    Abstract : Background: Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. Methods: Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. Results: OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1]; isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. Conclusions: OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.

  • Original Article2024-07-01 Diagnostic Hematology

    NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution

    Yu Jeong Choi , M.D., Ph.D., Young Kyu Min , Ph.D., Seung-Tae Lee , M.D., Ph.D., Jong Rak Choi , M.D., Ph.D., and Saeam Shin , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 335-342

    Abstract : Background: The three best-known NUP214 rearrangements found in leukemia (SET:: NUP214, NUP214::ABL1, and DEK::NUP214) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that NUP214 rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring NUP214 rearrangements. Methods: To identify patients with NUP214 rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted next-generation sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed. Results: In total, 11 patients harboring NUP214 rearrangements were identified, among whom four had SET::NUP214, three had DEK::NUP214, and four had NUP214::ABL1. All DEK::NUP214-positive patients were diagnosed as having AML. In patients carrying SET::NUP214 and NUP214::ABL1, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. PFH6 mutations were the most common (45.5%, 5/11), followed by WT1 (27.3%, 3/11), NOTCH1 (27.3%, 3/11), FLT3-internal tandem duplication (27.3%, 3/11), NRAS (18.2%, 2/11), and EZH2 (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of NUP214::ABL1-positive AML. Conclusions: We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.

  • Original Article2024-07-01 Diagnostic Genetics

    TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

    Hai-Yang Zhang , M.D., Feng-Yao Wu , M.D., Xue-Song Li , M.D., Ping-Hui Tu , M.D., Cao-Xu Zhang , M.D., Rui-Meng Yang , M.D., Ph.D., Ren-Jie Cui , Ph.D., Chen-Yang Wu , M.D., Ya Fang , M.D., Ph.D., Liu Yang , M.S., Huai-Dong Song , M.D., Ph.D., and Shuang-Xia Zhao , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 343-353

    Abstract : Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

  • Brief Communication2024-07-01 Diagnostic Hematology

    Comparison of Measurable Residual Disease in Pediatric B-Lymphoblastic Leukemia Using Multiparametric Flow Cytometry and Next-Generation Sequencing

    Sang Mee Hwang , M.D., Inseong Oh , M.D., Seok Ryun Kwon , M.D., Jee-Soo Lee , M.D., and Moon-Woo Seong , M.D.

    Ann Lab Med 2024; 44(4): 354-358

    Abstract : Measurable residual disease (MRD) testing, a standard procedure in B-lymphoblastic leukemia (B-ALL) diagnostics, is assessed using multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) analysis of immunoglobulin gene rearrangements. We evaluated the concordance between eight-color, two-tube MFC-MRD the LymphoTrack NGS-MRD assays using 139 follow-up samples from 54 pediatric patients with B-ALL. We also assessed the effect of hemodilution in MFC-MRD assays. The MRD-concordance rate was 79.9% (N=111), with 25 (18.0%) and 3 (2.2%) samples testing positive only by NGS-MRD (MFCNGS+MRD) and MFC-MRD (MFC+NGSMRD), respectively. We found a significant correlation in MRD values from total nucleated cells between the two methods (r=0.736 [0.647–0.806], P

  • Brief Communication2024-07-01 Transfusion and Cell Therapy

    Comparative Analysis of AB vs. ABO-specific Plasma for Desensitization in Blood Group O Recipients: An In Vitro Study

    Young Ae Lim , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 359-362

    Abstract : Neutralizing capacity measurement (NCM) of soluble ABH substances (SAS) in plasma was assessed to guide the selection of the appropriate ABO group of fresh-frozen plasma (FFP) for plasma exchange (PE) in blood group O recipients with ABO-incompatible transplantations. Neutralizing capacity was assessed by measuring anti-A and/or anti-B titers in samples comprising one unit of O FFP and 10 O EDTA plasma samples and subtracting the binary logarithm of the titer in each group with a saline dilution. Ten EDTA plasma samples with Lewis b (Leb) antigen positivity and 10 sets of pooled FFP from each blood group were used as diluents. In O FFP, the NCM values (mean±SD) were 3.4±0.52 (2.6±0.52) and 2.6±0.52 (1.5±0.3) in B and AB for IgM (total antibody) anti-B (both P

  • Letter to the Editor2024-07-01 Clinical Chemistry

    Direct LDL Cholesterol Assay vs. Estimated Equations in Patients With Hypertriglyceridemia or Low LDL Cholesterol Levels

    Jennifer Rodríguez-Domínguez , RD.J., Álvaro Piedra-Aguilera , PA.A., María Martínez-Bujidos , MB.M., Susana Malumbres-Serrano , MS.S., Cristian Morales-Indiano , MI.C., and Carla Fernández-Prendes , FP.C.

    Ann Lab Med 2024; 44(4): 363-366
  • Letter to the Editor2024-07-01 Clinical Chemistry

    Detection of a High-Dose Hook Effect and Evaluation of Dilutions of Urine Myoglobin Specimens Using a Serum Myoglobin Assay

    Joshua Joon Hyung Hunsaker , B.S., Sonia Leilani La’ulu, M.B.A., Emily Zupan, B.S., Dhwani Patel , B.S., Vrajesh Pandya , Ph.D., and Joseph William Rudolf , M.D.

    Ann Lab Med 2024; 44(4): 367-370
  • Letter to the Editor2024-07-01 Clinical Microbiology

    The First Case of Pulmonary Mucormycosis Caused by Lichtheimia ornata

    Jungjun Lee , M.D., Dong-Gun Lee , M.D., Ph.D., Raeseok Lee , M.D., M.P.H., Jae-Ho Yoon , M.D., Ph.D., Kyongmin Sarah Beck , M.D., Ph.D., In Young Yoo , M.D., Ph.D., and Yeon-Joon Park , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 371-374
  • Letter to the Editor2024-07-01 Clinical Microbiology

    A Severe Infection Caused by a White Colony-Producing Strain of Clostridioides difficile RTC41/ST588

    Se Yoon Park , M.D., Ph.D., Heejung Kim , M.D., Ph.D., and Yangsoon Lee , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 375-377
  • Letter to the Editor2024-07-01 Diagnostic Immunology

    Usefulness of Component-Resolved Diagnosis of Pollen-Food Allergy Syndrome

    Moon Won Lee , M.D., Hyun Ji Lee , M.D., Ph.D., Seulgi Moon , M.D., and Kyung-Hwa Shin , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 378-380
Annals of Laboratory Medicine
Journal Information July, 2024
Vol.44 No.4
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