1.Genomics of diffuse large B cell lymphoma
Blood Research 2021;56(S1):S75-S79
Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.
2.Genomics of diffuse large B cell lymphoma
Blood Research 2021;56(S1):S75-S79
Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.
3.AL amyloidosis: advances in diagnosis and management
Blood Research 2020;55(S1):S54-S57
Light chain (AL) amyloidosis is a disease in which malignant plasma cell clones affect multiple organs including the heart and kidney. The mechanism for organ function deterioration in AL amyloidosis differs from multiple myeloma. Thus, not all agents used to treat multiple myeloma shows similar efficacy in AL amyloidosis. In AL amyloidosis, both hematologic and organ responses after treatment are important to improve the clinical outcome. Especially, improving heart function is one of the key aspects in the treatment of AL amyloidosis. With recent advances in the understanding of the pathophysiologic mechanism of AL amyloidosis, novel treatment methods are under active trial. In this article, I have reviewed the advances in pathophysiology, diagnosis, risk stratification, and treatment of AL amyloidosis.
4.Physicians' preferences and perceptions regarding donor selection in allogeneic stem cell transplantation in Korea when a matched domestic donor is not available.
Min Kyung SHIN ; Sangjin SHIN ; Ja Youn LEE ; Youngil KOH
Blood Research 2017;52(1):31-36
BACKGROUND: A number of alternative donor options exist for patients who fail to find domestic HLA-matched donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed physicians' perspectives on allo-HSCT donor selection when a matched domestic donor is not available. METHODS: We administered a questionnaire survey to 55 hematologists (response rate: 28%) who attended the annual spring conference of the Korean Society of Haematology in 2015. The questionnaire contained four clinical allo-HSCT scenarios and the respondents were asked to choose the most preferred donor among the given options. RESULTS: In all four scenarios, the hematologists preferred a matched international donor over partially mismatched unrelated domestic or haplo-matched family donors. The numbers of hematologists who chose a matched international donor (HLA 8/8) in cases of acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, and aplastic anemia were 37 (67.3%), 41 (74.6%), 33 (60.0%), and 36 (65.5%), respectively. The important factors that affected donor selection included “expecting better clinical outcomes (40.5%)” and “lower risk of side effects (23.4%).” The majority of participants (80%) responded that allo-HSCT guidelines for donor selection customized for the Korean setting are necessary. CONCLUSION: Although hematologists still prefer perfectly matched foreign donors when a fully matched domestic allo-HSCT donor is not available, we confirmed that there was variation in their responses. For evidence-based clinical practice, it is necessary to provide further comparative clinical evidence on allo-HSCT from haplo-matched family donors and fully matched unrelated international donors.
Anemia, Aplastic
;
Donor Selection*
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
Korea*
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
;
Leukemia, Myeloid, Acute
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
Stem Cell Transplantation*
;
Stem Cells*
;
Surveys and Questionnaires
;
Tissue Donors*
;
Unrelated Donors
5.Peak Expiratory Flow Rate Underestimates Severity of Airflow Obstruction in Acute Asthma.
Inseon S CHOI ; Youngil I KOH ; Ho LIM
The Korean Journal of Internal Medicine 2002;17(3):174-179
BACKGROUND: Several investigators have demonstrated a considerable disagreement between FEV1 and PEFR to assess the severity of airflow obstruction. The purpose of this study was to examine whether the discrepancy between the two measurements affects the assessment in the severity of acute asthma. METHODS: Thirty-five consecutive asthma patients measured both FEV1 and PEFR at 0, 1hr, 1, 3, 5, 7 days of an emergency room admission using a spirometer and a Ferraris PEFR meter. The degree of discrepancy between FEV1 and PEFR expressed as % predicted values was determined. RESULTS: When predictive equations that recommended by the instrument manufacturers were used, PEFR measured with the PEFR meter (f-PEFR) was significantly higher than FEV1 at all time points, with 16.1% mean difference and unacceptable wide limits of agreement (-20.0~52.3%). The classification in severity was significantly different between FEV1 and f-PEFR (p < 0.001). The discrepancy was inter-instrumental in large part because f-PEFR was 10.1% higher than spirometric PEFR. Different predictive equations altered the degree of the differences but could not completely correct it. CONCLUSION: These results indicate that f-PEFR values underestimate the severity of airflow obstruction in acute asthma despite using recommended predictive equations. Therefore, these confounding factors should be considered when the severity of airflow obstruction is assessed with PEFR.
Acute Disease
;
Adult
;
Aged
;
Airway Obstruction/diagnosis/*physiopathology
;
Asthma/*physiopathology
;
Comparative Study
;
Female
;
Forced Expiratory Volume/physiology
;
Human
;
Male
;
Middle Age
;
Peak Expiratory Flow Rate/*physiology
;
Predictive Value of Tests
6.Two cases of vocal cord dysfunction.
Youngil I KOH ; Inseon S CHOI ; Seo Ung CHUNG
Korean Journal of Medicine 2004;67(Suppl 3):S902-S907
Vocal cord dysfunction (VCD), a condition that frequently mimics or confounds asthma, is characterized by a paradoxical adduction of the vocal cords on inspiration. The apposition of the vocal cords produces airflow obstruction sufficient to cause wheezing, chest tightness, shortness of breath, and cough. Misdiagnosis as asthma has led to inappropriate treatment, most notably with high-dose corticosteroids. Herein we report two cases of VCD who presented with chronic cough and episodic breathlessness, respectively. Flow-volume loops on spirometry were abnormal, with evidence of variable extrathoracic airway obstruction, manifested as flat or truncated inspiratory loops. Laryngoscopy or bronchoscopy demonstrated paradoxical adduction with posterior "chinking" of the vocal cords on inspiration. One case also had asthma and depressive illness. After the diagnosis of VCD, the clinical manifestations resolved with speech therapy and/or psychotherapy. VCD should be suspected in patients with asthma-like symptoms. An early diagnosis avoids unnecessary aggressive management.
Adrenal Cortex Hormones
;
Airway Obstruction
;
Asthma
;
Bronchoscopy
;
Cough
;
Diagnosis
;
Diagnostic Errors
;
Dyspnea
;
Early Diagnosis
;
Humans
;
Laryngoscopy
;
Psychotherapy
;
Respiratory Sounds
;
Speech Therapy
;
Spirometry
;
Thorax
;
Vocal Cord Dysfunction*
;
Vocal Cords*
7.The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes
Tae Jung OH ; Han SONG ; Youngil KOH ; Sung Hee CHOI
Endocrinology and Metabolism 2022;37(2):243-248
Background:
Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN).
Methods:
This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN.
Results:
CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level.
Conclusion
On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.
8.Effects of Somatic Mutations Are Associated with SNP in the Progression of Individual Acute Myeloid Leukemia Patient: The Two-Hit Theory Explains Inherited Predisposition to Pathogenesis.
Soyoung PARK ; Youngil KOH ; Sung Soo YOON
Genomics & Informatics 2013;11(1):34-37
This study evaluated the effects of somatic mutations and single nucleotide polymorphisms (SNPs) on disease progression and tried to verify the two-hit theory in cancer pathogenesis. To address this issue, SNP analysis was performed using the UCSC hg19 program in 10 acute myeloid leukemia patients (samples, G1 to G10), and somatic mutations were identified in the same tumor sample using SomaticSniper and VarScan2. SNPs in KRAS were detected in 4 out of 10 different individuals, and those of DNMT3A were detected in 5 of the same patient cohort. In 2 patients, both KRAS and DNMT3A were detected simultaneously. A somatic mutation in IDH2 was detected in these 2 patients. One of the patients had an additional mutation in FLT3, while the other patient had an NPM1 mutation. The patient with an FLT3 mutation relapsed shortly after attaining remission, while the other patient with the NPM1 mutation did not suffer a relapse. Our results indicate that SNPs with additional somatic mutations affect the prognosis of AML.
Cohort Studies
;
Disease Progression
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Leukemia, Myeloid, Acute
;
Point Mutation
;
Polymorphism, Single Nucleotide
;
Prognosis
;
Recurrence
9.Upper airway hyperresponsiveness To methacholine in patients with suspected asthma.
Inseon S CHOI ; Kwang Won KANG ; Youngil I KOH ; Seo Na HONG
Journal of Asthma, Allergy and Clinical Immunology 2002;22(3):540-547
BACKGROUND: Upper airway diseases, such as vocal cord dysfunction (VCD), masquerade as asthma. Bronchial hyperresponsiveness (BHR) to methacholine (MCh) has been demonstrated in only part of suspected asthma patients. Investigators have shown upper airway hyperresponsi- veness (UHR) in patients with VCD. OBJECTIVE: To determine the clinical importance of UHR and to evaluate the usefulness of UHR test in patients with suspected asthma. METHODS: Thirty-six consecutive patients with suspected asthma underwent a MCh inhalation challenge. BHR was determined with PC20 < 8 mg/ml, UHR with a decrease in MIF50 > 25% from the baseline, and upper airway obstruction (UAO) with MEF50/MIF50 > 1. RESULTS: Only 17 patients (47.2%) showed BHR. Also, the same proportion of subjects showed UHR, and the each combination of BHR/UHR was nearly equal in distribution (9 BHR+/UHR-, 8 BHR+/UHR+, 9 BHR-/UHR+, and 10 BHR-/UHR-). Patients with BHR-/UHR+ had significantly lower serum total IgE level than those with BHR-/UHR-. Eight patients with UHR and UAO showed significantly shorter duration of disease (p < 0.05), smaller numbers of atopy family history (p < 0.05), and lower serum total IgE level than the others (p < 0.05). CONCLUSION: Many patients with suspected asthma showed UHR, and about half of patients with negative MCh-BHR showed UHR that might be related to non-asthmatic diseases including VCD. Therefore, a routine UHR test may be warranted in detecting upper airway diseases in suspected asthma.
Airway Obstruction
;
Asthma*
;
Humans
;
Immunoglobulin E
;
Inhalation
;
Methacholine Chloride*
;
Research Personnel
;
Vocal Cord Dysfunction
10.Effects of Cytokine Milieu Secreted by BCG-treated Dendritic Cells on Allergen-Specific Th Immune Response.
Youngil I KOH ; Inseon S CHOI ; Je Jung LEE
Journal of Korean Medical Science 2004;19(5):640-646
Bacillus Calmette-Guerin (BCG) is reported to suppress Th2 response and asthmatic reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections with BCG are known to result in inducing various cytokines. Thus, DCs are likely to play a role in the effects of BCG on asthma. This study aims at investigating that cytokine milieu secreted by BCG-treated DCs directly enhances allergen-specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics. DCs were cultured with and without BCG and subjected to flow cytometric analysis. IL-12 and IL-10 were determined from the culture supernatants. Some DCs were cocultured with T cells in the presence of D. farinae extracts after adding the culture supernatants from BCG-treated DCs, and IL-5 and IFN-gamma were determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86, and CD40, and the productions of IL-12 and IL-10. Addition of culture supernatants from BCG-treated DCs up-regulated production of IFN-gamma by T cells stimulated by DCs and D. farinae extracts (p<0.05), but did not down-regulate production of IL-5 (p>0.05). The cytokine milieu secreted by BCG-treated DCs directly enhanced allergen-specific Th1 response, although did not suppress Th2 response.
Antigens, Dermatophagoides/*immunology
;
Asthma/*immunology
;
Cells, Cultured
;
Coculture Techniques
;
Culture Media
;
Cytokines/*immunology/secretion
;
Dendritic Cells/cytology/*immunology/secretion
;
Humans
;
Hypersensitivity/immunology
;
Interferon Type II/immunology/secretion
;
Interleukin-10/immunology/secretion
;
Interleukin-12/immunology/secretion
;
Interleukin-5/immunology/secretion
;
Lymphocyte Activation/immunology
;
Mycobacterium bovis/*immunology
;
Research Support, Non-U.S. Gov't
;
Th2 Cells/cytology/immunology/secretion
;
Up-Regulation/immunology