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1.
Article in English | WPRIM | ID: wpr-915524

ABSTRACT

Background@#In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. @*Methods@#A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. @*Results@#A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). @*Conclusion@#This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

2.
Article in English | WPRIM | ID: wpr-914058

ABSTRACT

Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3Rmutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis.Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.

3.
Blood Research ; : 301-314, 2021.
Article in English | WPRIM | ID: wpr-913720

ABSTRACT

Background@#In this study, we presented the national cancer statistics on the incidence of hematologic malignancies in the Republic of Korea (ROK) over a period of 20 years, from 1999 to 2018. @*Methods@#We obtained data on the incidence of hematologic malignancies using the Korean Statistical Information Service (KOSIS). For each hematologic malignancy, the number of cases, crude incidence rate, and age-standardized incidence rate were calculated, and the statistical trends were confirmed by Poisson regression and Joinpoint regression analysis. @*Results@#All the investigated hematologic malignancies showed a statistically significant increase in incidence over 20 years. The 20-year trend of the age-standardized incidence rate was as follows: non-Hodgkin lymphoma [average annual percent change (AAPC)=2.26%, P-trend <0.05], leukemia (AAPC=0.94%, P-trend <0.05), myeloid leukemia (AAPC=1.44%, P-trend <0.05), multiple myeloma (AAPC=3.05%, P-trend <0.05), myeloproliferative disorders (AAPC=9.87%, P-trend <0.05), myelodysplastic syndrome (AAPC=7.59%, P-trend <0.05), malignant immunoproliferative diseases (AAPC=11.82%, P-trend <0.05), lymphoid leukemia (AAPC=2.21%, P-trend <0.05), and Hodgkin lymphoma (AAPC=4.04%, P <0.05). @*Conclusion@#It was confirmed that the incidence of hematologic malignancies has increased significantly in the ROK over the past 20 years. This study can be used as foundational data source for future studies. In addition, it can aid in the necessary actions of predicting future incidences and establishing future healthcare policies.

4.
Article in English | WPRIM | ID: wpr-874172

ABSTRACT

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l’Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 Aspergillus (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed “no identification” or “multiple species identification” results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for Aspergillus, dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed “no identification” and “misidentification” results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification

5.
Article in English | WPRIM | ID: wpr-874171

ABSTRACT

Stool examination is the gold standard for the detection of intestinal parasites. We assessed the performance of a newly developed AVE-562 analyzer (AVE Science & Technology Co., Hunan, China) for the vision-based detection of eggs of Clonorchis sinensis—the most common intestinal parasite in Korea—in stool samples. In total, 30 stool samples with a high or low egg count or without eggs (as negative control samples) (N = 10 each) were prepared and analyzed. The performance of the AVE-562 analyzer was compared with that of the formalin-ether concentration (FEC) method. The overall correct identification rate of the AVE-562 analyzer based on FEC results was 66.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of the AVE-562 analyzer for detecting C. sinensis eggs were 36.4%, 100.0%, 100.0%, and 73.1%, respectively. The average time required to run five tests simultaneously was 27 min using the AVE-562 analyzer and 58 min using the FEC method. Although the AVE-562 analyzer enables rapid and convenient stool examination, its sensitivity needs to be improved, particularly considering the prevalence of low-burden C. sinensis infection in Korea.

6.
Article in English | WPRIM | ID: wpr-874149

ABSTRACT

Phospholipase C beta 2 (PLC-β2) regulates various essential functions in cell signaling, differentiation, growth, and mobility. We investigated the clinical implications of PLC-β2 protein expression in newly diagnosed normal karyotype acute myeloid leukemia (NKAML). The PLC-β2 expression status in bone marrow tissues obtained from 101 patients with NK-AML was determined using semiquantitative immunohistochemistry (IHC). IHC results were compared with those for known prognostic markers. Using a cutoff score for positivity of 7.0, the PLC-β2 overexpression group showed superior overall survival (OS) (72.6% vs. 26.5%; P = 0.016) and low hazard ratio (HR) (0.453; P = 0.019) compared with the PLC-β2 low-expression group. The PLC-β2 overexpression group showed no significant gain in event-free survival (50.6% vs. 43.0%, P =0.465) and HR (0.735; P =0.464).Among the known prognostic markers, only FLT3-ITD positivity was associated with a significantly low OS and high HR. In conclusion, PLC-β2 overexpression was associated with favorable OS in NK-AML patients. Our results suggest that PLC-β2 expression assessment using IHC allows prognosis prediction in NK-AML.

8.
Article in English | WPRIM | ID: wpr-762467

ABSTRACT

No abstract available.


Subject(s)
Candida , Fungemia
9.
Blood Research ; : 225-245, 2020.
Article in English | WPRIM | ID: wpr-889635

ABSTRACT

Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.

10.
Blood Research ; : 225-245, 2020.
Article in English | WPRIM | ID: wpr-897339

ABSTRACT

Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.

11.
Laboratory Medicine Online ; : 214-220, 2020.
Article | WPRIM | ID: wpr-836922

ABSTRACT

Background@#Prohibitin (PHB) regulates intracellular signal pathways, transcription, and cell cycles. Aberrant expression of the PHB gene is known to be related totumorigenesis, tumor progression, and chronic metabolic and inflammatory diseases. The present study aimed to develop a one-step quantitative reverse transcription PCR (RT-qPCR) kit for quantifying PHB mRNA levels and evaluate its performance in the laboratory. @*Methods@#TaqMan chemistry was used to develop the one-step PHB1 and PHB2 RT-qPCR kit. Normal peripheral blood cells from healthy individuals (N=20) and leukemia cells from patients initially diagnosed with acute myeloid leukemia (AML, N=20), chronic myeloid leukemia (CML, N=13), and acute lymphoid leukemia (ALL, N=7) were enrolled to evaluate the laboratory performance of the kit using commercially available total human RNA controls. @*Results@#The intra-assay and inter-assay precision of the kit developed in this study was less than 2%. The distribution of PHB1 mRNA expression of AML, CML, and ALL was 0.898-0.993 (median: 0.936), 0.817-0.976 (0.918), and 0.844-1.074 (0.973), respectively. The distribution of PHB2 mRNA expression of AML, CML, and ALL was 0.957-1.024 (median: 0.985), 0.988-1.047 (1.002), and 0.937-1.059 (1.004), respectively. The sensitivity, specificity, positive and negative predictive value, and test effectiveness of the developed PHB1 and PHB2 kit were greater than 50% for each parameter. @*Conclusions@#Our developed kit would be useful for diagnosing leukemia as well as detecting residual disease. Additionally, this kit could be used for monitoring and conducting molecular pathophysiological studies of obesity, metabolic, and inflammatory diseases.

12.
Article in Korean | WPRIM | ID: wpr-759588

ABSTRACT

D antigens are clinically significant, and routine tests on the D antigen requires the inclusion of weak D testing, which is performed using indirect antihuman immunoglobulin methods. On the other hand, exact typing of the D type of an individual can be done more precisely with RHD genotyping, which is a useful tool in cases where the RHD gene is intact. The majority of weak-D or partial-D cases are from single nucleotide changes or hybridization of RHD and RHCE genes. Nevertheless, frameshift mutations can also result in weak or partial-D. The characteristics of a frameshift mutation is typically a change in protein product after a problematic mutation and early termination of transcription, leading into truncated protein products. This paper reports a D-variant case with RHD 711delC along with a review of the relevant literature. In addition, the results of software analysis are reported.


Subject(s)
Frameshift Mutation , Genotype , Hand , Immunoglobulins
13.
Blood Research ; : 253-261, 2019.
Article in English | WPRIM | ID: wpr-785541

ABSTRACT

BACKGROUND: Fluoranthene (FR) is a common environmental pollutant that exists in a complex mixture with other polycyclic aromatic hydrocarbons (PAHs). We identified biomarkers for monitoring FR exposure and investigated the rescue effect of FR-induced cellular toxicity via aryl hydrocarbon receptor (AHR) antagonist activity in bone marrow derived mesenchymal stem cells (BM-MSCs).METHODS: Morphological changes, viability, and rescue effects of an AHR antagonist (CH223191) were examined in BM-MSCs after exposure to FR. Cytotoxic effects were assayed using the tetrazolium-based colorimetric assay. Apoptosis was measured by annexin V and propidium iodide dye-based flowcytometry assay, mitochondrial membrane potential assay, and nuclear DNA fragmentation assay. Molecular signaling pathways of apoptosis and autophagy were investigated using immunoblotting. Proteomics were performed in order to reveal the spectra of cellular damage and identify biomarkers for FR exposure.RESULTS: Exposing BM-MSCs to FR (IC₅₀=50 µM) induced cell death and morphological changes, while the AHR antagonist showed rescue effects. Autophagy was activated and mitochondrial membrane potential was decreased. Proteomic analysis identified 48 deregulated proteins (26 upregulated and 22 downregulated). Among them, annexin A6, pyruvate kinase, UDP-glucose dehydrogenase, and phospholipase A2 could be potential biomarkers for FR exposure.CONCLUSION: The exposure of BM-MSCs to FR induced remarkable alterations in cellular biology and the proteome, allowing for identification of novel biomarkers for FR exposure. Furthermore, AHR antagonists might be able to prevent cellular damage due to FR exposure.


Subject(s)
Annexin A5 , Annexin A6 , Apoptosis , Autophagy , Biomarkers , Bone Marrow , Cell Death , DNA Fragmentation , Immunoblotting , Membrane Potential, Mitochondrial , Mesenchymal Stem Cells , Oxidoreductases , Phospholipases A2 , Polycyclic Aromatic Hydrocarbons , Propidium , Proteome , Proteomics , Pyruvate Kinase , Receptors, Aryl Hydrocarbon
15.
16.
Article in English | WPRIM | ID: wpr-718329

ABSTRACT

BACKGROUND: Serum copeptin has been demonstrated to be useful in early risk stratification and prognostication of patients with acute myocardial infarction (AMI). However, the prognostic value of copeptin after percutaneous coronary intervention (PCI) for clinical outcomes remains uncertain. We investigated the prognostic role of serum copeptin levels immediately after successful PCI as a prognostic marker for major adverse cardiac events (MACE; comprising death, repeat PCI, recurrent MI, or coronary artery bypass grafting) in patients with AMI. METHODS: A retrospective study was performed in 149 patients with AMI who successfully received PCI. Serum copeptin levels were analyzed in blood samples collected immediately after PCI. The association between copeptin levels and MACE during the follow-up period was evaluated. RESULTS: MACE occurred in 34 (22.8%) patients during a median follow-up of 30.1 months. MACE patients had higher copeptin levels than non-MACE patients did. Multiple logistic regression analysis showed that the increase in serum copeptin levels was associated with increased MACE incidence (odds ratio=1.6, P=0.005). CONCLUSIONS: A high level of serum copeptin measured immediately after PCI was associated with MACE in patients with AMI during long-term follow-up. Serum copeptin levels can serve as a prognostic marker in patients with AMI after successful PCI.


Subject(s)
Coronary Artery Bypass , Follow-Up Studies , Humans , Incidence , Logistic Models , Myocardial Infarction , Percutaneous Coronary Intervention , Prognosis , Retrospective Studies
17.
Article in English | WPRIM | ID: wpr-717062

ABSTRACT

Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.


Subject(s)
Adenosine Triphosphate , Adult , Adult Stem Cells , Aging , Animals , Bone Marrow , Cell Respiration , Cytoplasm , Diet , Dietary Supplements , Hematologic Neoplasms , Hematopoiesis , Hematopoietic Stem Cells , Humans , Immune System , Incidence , Membrane Potentials , Mice , Mitochondria , Niacin , Niacinamide , Phenotype , Sirtuins , Stem Cells , Tryptophan , Vitamins
18.
Article in English | WPRIM | ID: wpr-717647

ABSTRACT

BACKGROUND: Few studies of high dose dexamethasone (HD-DXM) therapy in children with immune thrombocytopenic purpura (ITP) have been reported. The purpose of this study is to investigate efficacy and safety of repeated HD-DXM therapy as second-line treatment of ITP in childhood. METHODS: We retrospectively analyzed the medical records of patients < 18 years of age with primary ITP who received more than 2 cycles of HD-DXM therapy from May 2004 to January 2018. HD-DXM was given orally in 4-day pulses every 28 days as a 20–40 mg/1.73 m² daily dose. RESULTS: A total of 26 patients (male, 19; female, 7) were enrolled and their median age was 6 years (range, 1–15). All patients had received previous treatment for ITP. A median 6 cycles (range, 2–19) of HD-DXM was given. On the beginning of HD-DXM therapy, three patients satisfied the criteria for newly diagnosed ITP, 16 for persistent ITP and 7 for chronic ITP. Relapse-free survival (RFS) of responders (n=9) after the last HD-DXM cycle was estimated to be 38.1±17.2%, lasting for a median 9.1 months (range, 5.6–46.2). According to response after the 2nd cycle, RFS of responders (n=13) was significantly higher than non-responders (23.1±11.7% vs. 7.7%±7.4%, P=0.001). The most common adverse event was irritability (30.8%), followed by fatigue (19.2%). CONCLUSION: HD-DXM therapy in children was relatively tolerated and response after therapy was acceptable. More courses of HD-DXM may be feasible in responders after two cycles of HD-DXM.


Subject(s)
Child , Dexamethasone , Fatigue , Female , Humans , Medical Records , Purpura, Thrombocytopenic, Idiopathic , Retrospective Studies
19.
Article in Korean | WPRIM | ID: wpr-760480

ABSTRACT

BACKGROUND: Whole blood viscosity (WBV) refers to the internal resistance that occurs when blood flows through blood vessels. WBV is known to be related to many diseases including cardiovascular and neurovascular diseases. We have investigated the analytical performance and established reference intervals for a newly developed microfluidic viscometer, Viscore-300 (NanoBiz, Korea), used for the measurement of WBV. METHODS: We performed a precision test of 240 measurements over 20 days using three control materials. For evaluation of repeatability, a total of 60 WBV measurements were made in 3 whole blood samples 20 times a day. A total of 100 whole blood samples were used to evaluate the accuracy of the Viscore-300 in comparison to a rotating viscometer, DV3T (Brookfield, USA), in accordance with the the Clinical and Laboratory Standards Institute's guidelines. To establish the reference intervals, 122 healthy individuals were enrolled in this study. RESULTS: The precision and repeatability results showed that the CV was less than 5% for three samples and two shear rates. In the accuracy test, the mean differences between two viscometers were 0.09 cP (0.9%) and −0.07 cP (−1.4%) at shear rates of 10 s−1 and 300 s−1, respectively. The reference intervals of WBV for men were 6.88–13.52 cP at 10 s−1 and 4.32–6.43 cP at 300 s−1; those of women were 5.74–13.29 cP at 10 s−1 and 3.60–6.12 cP at 300 s−1. CONCLUSIONS: Viscore-300 showed excellent precision and accuracy and it might be a good instrument for reporting WBV quickly and accurately.


Subject(s)
Blood Vessels , Blood Viscosity , Female , Humans , Male , Microfluidics
20.
Article in English | WPRIM | ID: wpr-760477

ABSTRACT

This study aimed to survey the status of quality control (QC) assurance for stool examinations at clinical laboratories in Korea. We sent a questionnaire related to QC practices in stool examination by electronic mail to Korean clinical laboratories that performed stool examination. Overall, 20 of the 39 laboratories (51.3%) reported performing stool concentration methods, and 28 (71.8%) examined the slides using only saline. A large proportion (74.4%) of respondents did not check the internal QC because of the restriction of appropriate control materials. Only four laboratories (10.3%) checked the reactivity of the dye solution routinely. For appropriate external QC systems, QC slides (43.6%) were preferred, followed by QC materials (30.8%), virtual slides (17.9%), and a combination of the above options (7.7%). The most commonly observed parasites in stool samples at the clinical laboratories were Clonorchis sinensis (75%), followed by Endolimax nana, Enterobius vermicularis, and Entamoeba coli. The present study describes the difficulties in internal QC assessment due to the absence of standardized QC materials and systems. We hope the findings of this report will provide a foundation for a QC assessment program for stool examinations in the near future.


Subject(s)
Clonorchis sinensis , Electronic Mail , Endolimax , Entamoeba , Enterobius , Hope , Korea , Parasites , Quality Control , Surveys and Questionnaires
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