Impact of Genetic Abnormalities on the Prognoses and Clinical Parameters of Patients with Multiple Myeloma

제갈동욱,김명신,Ahlm Kwon,김현정,채효진,민창기,임지향,김용구,한경자 대한진단검사의학회 2013 Annals of Laboratory Medicine Vol.33 No.4

Background: We reviewed patients with multiple myeloma (MM) in order to assess the incidence of genetic abnormalities and their associations with clinical parameters, risk groups, and prognosis. Methods: A total of 130 patients with MM were enrolled. The incidences of genetic abnormalities were determined in all patients. The relationships of the genetic abnormalities and clinical parameters were investigated. In addition, a survival analysis was performed. Results: Abnormal karyotypes were detected in 42.3% (N=55) of the patients, and this was increased to 63.1% (N=82) after including the results determined with interphase FISH. Hypodiploidy was observed in 7.7% (N=10) of the patients, and all were included in the group with complex karyotypes (30.8%, N=40). The 14q32 rearrangements were detected in 29.2% (N=38) of the patients, and these most commonly included t(11;14),which was followed by t(4;14) and t(14;16) (16.2%, 11.5%, and 0.8%, respectively). Abnormal karyotypes and complex karyotypes were associated with disease progression markers, including low hemoglobin levels, low platelet counts, high plasma cell burden,high β2-microglobulin, and high international staging system stages. A high free light chain (FLC) ratio and FLC difference were associated with abnormal karyotypes, complex karyotypes, and higher plasma cell burden. Hypodiploidy and low platelet counts were significant independent prognostic factors and were more important in patient outcome than any single abnormality. Conclusions: Genetic abnormalities were associated with disease progression markers and prognosis of MM patients.

Characteristics of DNMT3A mutations in acute myeloid leukemia

Dong Jin Park,Ahlm Kwon,Byung-Sik Cho,Hee-Je Kim,Kyung-Ah Hwang,Myungshin Kim,Yonggoo Kim 대한혈액학회 2020 Blood Research Vol.55 No.1

DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hema-topoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clin-ical significance in AML and their influence on promoter methylation and CDKN2Bexpression.MethodsA total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using py-rosequencing and RT-qPCR.ResultsWe identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8‒23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3Amutations. CDKN2B expression inversely correlated with CDKN2B promoter methyl-ation and was significantly higher in AML with R882H mutation in DNMT3A. We demon-strated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent un-favorable prognostic factor after multivariate analysis.ConclusionWe characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.

Targeted Next-Generation Sequencing of Plasma Cell-Free DNA in Korean Patients with Hepatocellular Carcinoma

Chae Hyojin,Sung Pil Soo,Choi Hayoung,Kwon Ahlm,Kang Dain,Kim Yonggoo,Kim Myungshin,Yoon Seung Kew 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.2

Background: Hepatocellular carcinoma (HCC) is the second-most-common cause of cancer-related deaths worldwide, and an accurate and non-invasive biomarker for the early detection and monitoring of HCC is required. We assessed pathogenic variants of HCC driver genes in cell-free DNA (cfDNA) from HCC patients who had not undergone systemic therapy. Methods: Plasma cfDNA was collected from 20 HCC patients, and deep sequencing was performed using a customized cfDNA next-generation sequencing panel, targeting the major HCC driver genes (TP53, CTNNB1, TERT) that incorporates molecular barcoding. Results: In 13/20 (65%) patients, we identified at least one pathogenic variant of two major HCC driver genes (TP53 and CTNNB1), including 16 variants of TP53 and nine variants of CTNNB1. The TP53 and CTNNB1 variants showed low allele frequencies, with median values of 0.17% (range: 0.06%-6.99%) and 0.07% (range: 0.05%–0.96%), respectively. However, the molecular coverage of variants was sufficient, with median values of 5,543 (range: 2,317–9,088) and 7,568 (range: 2,400–9,633) for TP53 and CTNNB1 variants, respectively. Conclusions: Our targeted DNA sequencing successfully identified low-frequency pathogenic variants in the cfDNA from HCC patients by achieving high coverage of unique molecular families. Our results support the utility of cfDNA analysis to identify somatic gene variants in HCC patients.

Isolation and Characterization of Chorionic Mesenchymal Stromal Cells from Human Full Term Placenta

구보경,박인양,Jiyeon Kim,Ji-Hyun Kim,Ahlm Kwon,김명신,김용구,신종철,김종훈 대한의학회 2012 Journal of Korean medical science Vol.27 No.8

This study focused on the characterization of mesenchymal stromal cells (MSCs) from the chorion of human full term placenta from 15 donors. Chorionic MSCs revealed homologous fibroblast-like morphology and expressed CD73, CD29, CD105, and CD90. The hematopoietic stem cell markers including HLA DR, CD11b, CD34, CD79a, and CD45were not expressed. The growth kinetics of their serial passage was steady at the later passages (passage 10). The multilineage capability of chorionic MSCs was demonstrated by successful adipogenic, osteogenic and chondrogenic differentiation and associated gene expression. Chorionic MSCs expressed genes associated with undifferentiated cells (NANOG, OCT4, REX1) and cardiogenic or neurogenic markers such as SOX2, FGF4, NES,MAP2, and NF. TERT was negative in all the samples. These findings suggest that chorionic MSCs undifferentiated stem cells and less likely to be transformed into cancer cells. A low HLA DR expression suggests that chorionic MSCs may serve as a great source of stem cells for transplantation because of their immune-privileged status and their immunosuppressive effect. Based on these unique properties, it is concluded that chorionic MSCs are pluripotent stem cells that are probably less differentiated than BM-MSCs, and they have considerable potential for use in cell-based therapies.

OB-40 : Isolation and Characterization of Chorionic Mesenchymal Stromal Cells from Human Full Term Placenta

( Hye Jung Yun ),( Ju Young Cheon ),( Narinay Kim ),( In Yang Park ),( Bo Kyung Koo ),( Jiyeon Kim ),( Ji Hyun Kim ),( Ahlm Kwon,),( Myungshin Kim ),( Yonggoo Kim ),( Jong Chul Shin ),( Jong Hoon Kim 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-

목적: Adult stem cells are considered as an excellent source for research because they pose few ethical problems and limitations in terms of availability. Although many types of stem cells are available, the sources of the stem cells selected for clinical use should possess the ability to renew, be easily isolated and be pluripotent. These properties can be satisfied with human term placental-derived stromal cells. It is essential to understand the expansion capability and potency of isolated stem cells. 방법: This study focused on the characterization of mesenchymal stromal cells (MSCs) from the chorion of human full term placenta from 15 donors.We characterized the surface markers and multilineage differentiation (adipogenic, osteogenic and chondrogenic induction) ability of cultured chorionic MSCs. We also present our findings regarding their growth rate and gene expressions. 결과: Chorionic MSCs revealed homologous fibroblast-like morphology and expressed CD73, CD29, CD105, and CD90. The hematopoietic stem cell markers including HLA DR, CD11b, CD34, CD79a, and CD45 were not expressed. The growth kinetics of their serial passage was steady at the later passages (passage 10). The multilineage capability of chorionic MSCs was demonstrated by successful adipogenic, osteogenic and chondrogenic differentiation and associated gene expression. Chorionic MSCs expressed genes associated with undifferentiated cells (NANOG, OCT4, REX1) and cardiogenic or neurogenic markers such as SOX2, FGF4, NES, MAP2, and NF. TERT was negative in all the samples. 결론: A low HLA DR expression suggests that chorionic MSCs may serve as a great source of stem cells for transplantation because of their immune- privileged status and their immunosuppressive effect. Based on these unique properties, it is concluded that chorionic MSCs are pluripotent stem cells that are probably less differentiated than BM-MSCs, and they have considerable potential for use in cell-based therapies.