1.Clonal Burden, Immunoglobulin Heavy Chain Variable Gene Somatic Hypermutations, and Immunoglobulin Gene Repertoire in Korean Patients with Chronic Lymphocytic Leukemia Assessed by Next-Generation Sequencing
Taegeun LEE ; Daehyun CHU ; Miyoung KIM ; Young-Uk CHO ; Sang-Hyun HWANG ; Jung-Hee LEE ; Dok Hyun YOON ; Hyungwoo CHO ; Seongsoo JANG
Annals of Laboratory Medicine 2026;46(2):136-145
Background:
We compared the immunoglobulin (IG) heavy chain (IGH) leader and FR1 primer sets to measure clone sizes and detect immunoglobulin heavy chain variable (IGHV) region somatic hypermutations (SHMs) in Korean patients with chronic lymphocytic leukemia (CLL). We also analyzed IGH and immunoglobulin kappa (IGK) to identify Korean-specific IGs in CLL.
Methods:
Next-generation sequencing (NGS)–based gene rearrangements and IGHV SHMs were assessed in 40 patients using IGH leader, IGH FR1, and IGK primers. Flow cytometry, karyotyping, interphase FISH, and NGS-based variant analyses were performed for 165 genes.
Results:
Clonal IGH and IGK rearrangements were detected in 100.0% and 97.5% of patients, respectively. Clonal size was generally smaller per NGS than per flow cytometry, particularly when using the IGH leader (median: 52.5%) versus the IGH FR1 primer set (73.2%). IGHV SHMs occurred in approximately 70% of patients; 10% showed primer set discrepancies. The incidence of IGHV SHMs was low in patients at high risk (i.e., with TP53 abnormalities; complex karyotypes; and ATM, NOTCH1, SF3B1, or BIRC3 variants). IGHV3 was the most common IGHV (58.3%), and IGHV4-34 was most frequently identified (14.6%). IGHV1 and IGHV1-69 usage differed significantly between Koreans and westerners. IGHJ4 was the most common IGHJ (56.3%). A single IGKV–IGKJ gene rearrangement was most frequently observed (18.9%), whereas intron-KDE was the most common rearrangement (30.6%).
Conclusions
NGS may underestimate CLL clonal size, particularly when using the IGH leader primer set. IGHV SHMs were inversely associated with negative prognostic factors.Our data suggest ethnic differences in CLL pathogenesis.
2.Improved survival in pediatric acute lymphoblastic leukemia through therapy intensification based on minimal residual disease and protocol‑driven early response risk classification
Hyery KIM ; Su Hyun YOON ; Sunghan KANG ; Kyung‑Nam KOH ; Ho Joon IM ; Daehyun CHU ; Mi Young KIM ; Young‑Uk CHO ; Sang‑Hyun HWANG ; Seongsoo JANG
Blood Research 2025;60():40-
Purpose:
Minimal residual disease (MRD)-guided therapy is the global standard treatment for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification along with protocol-defined risk groups in pediatric ALL treatment.
Methods:
This retrospective analysis included 209 patients with ALL (treated between January 2013 to June 2023).MRD was assessed using six- to eight-color flow cytometry at the end of each phase before the maintenance phase.Post-induction treatment was determined based on early response, National Cancer Institute risk, and cytogenet‑ ics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols and standard-risk (SR) patients followed the modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified.
Results:
Overall, 103 and 106 patients were classified as having SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3%, respectively. Thirty SR and 18 HR patients received intensi‑ fied chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs. 75.5%, p = 0.04), particularly in post-induction patients with high MRD (90.0% vs. 19.0%, p = 0.035). The difference in survival between rapid early responder (RER) and slow early responder (SER) groups was eliminated after MRD-based intensifi‑ cation. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% during 2016– 2019, and 13.9% during 2020–2023), reflecting improved risk stratification and therapy selection.
Conclusion
MRD-guided therapy intensification markedly improved survival outcomes in patients with pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing riskadapted treatment strategies.
3.Usefulness of Additional LISS/Coombs Card Test with Enzyme-Treated Red Cells in Detecting Anti-Kidd Antibodies Not Detectable by NaCl/Enzyme Card Test Alone.
Daehyun CHU ; Soo Jung PARK ; Suk Won SEO ; Hoi Joo YANG ; Yousun CHUNG ; Seog Woon KWON
Korean Journal of Blood Transfusion 2016;27(1):31-37
BACKGROUND: Detection of anti-Kidd antibody is important because of its clinical significance. If detection is difficult due to weak serological reactivity or dosage effect, use of an enzyme method could be helpful. However, despite use of an enzyme method, we still observed weak reactivity of anti-Kidd antibody. METHODS: All identified anti-Kidd antibody cases from Jan 2012 to Aug 2015 in Asan Medical Center were reviewed. Antibody identification test was performed using the column agglutination technique using Bio-Rad ID-DiaPanel with LISS/Coombs card, Bio-Rad ID-DiaPanel-P with NaCl/Enzyme card, and ID-DiaPanel-P with LISS/Coombs card. The test results were compared. RESULTS: Sixty cases of anti-JK(a) or anti-Jk(b) were detected and tested by enzyme method. Among them, 34 (56.6%) cases showed strengthened reactivity using the ID-DiaPanel-P with NaCl/Enzyme card method. However, 26 (43.4%) cases showed weakened reactivity. Of these, 13 cases that could be tested by an additional method using ID-DiaPanel-P with LISS/Coombs card containing anti-IgG and anti-C3d showed successfully strengthened reactivity. CONCLUSION: The reactivity of anti-Kidd antibodies that was not strengthened using ID-DiaPanel-P with NaCl/Enzyme card method could be successfully strengthened by use of the ID-DiaPanel-P with LISS/Coombs card.
Agglutination
;
Antibodies*
;
Chungcheongnam-do
4.Straightforward Identification of Masked Polycythemia Vera Based on Proposed Revision of World Health Organization Diagnostic Criteria for BCR-ABL1-Negative Myeloproliferative Neoplasms.
Daehyun CHU ; Young Uk CHO ; Seongsoo JANG ; Eul Ju SEO ; Chan Jeoung PARK
Annals of Laboratory Medicine 2015;35(6):651-653
No abstract available.
Adult
;
Biomarkers, Tumor/genetics
;
Bone Marrow/pathology
;
Calreticulin/genetics
;
Erythropoietin/blood
;
Female
;
Fusion Proteins, bcr-abl/*genetics
;
Hematocrit
;
Hemoglobins/analysis
;
Humans
;
Janus Kinase 2/genetics
;
Male
;
Middle Aged
;
Mutation
;
Myeloproliferative Disorders/*diagnosis/genetics
;
Polycythemia Vera/*diagnosis/genetics
;
Receptors, Thrombopoietin/genetics
;
Thrombocythemia, Essential/diagnosis
;
World Health Organization

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