ABSTRACT
Background@#Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD. @*Methods@#GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject. @*Results@#The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1. @*Conclusion@#Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.
ABSTRACT
Background@#Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD. @*Methods@#GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject. @*Results@#The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1. @*Conclusion@#Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.
ABSTRACT
BACKGROUND: A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings. METHODS: Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined. RESULTS: Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11-20% in 14 patients, 21-30% in 3 patients, 31-40% in 4 patients, 41-50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033). CONCLUSION: The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.
Subject(s)
Humans , Biopsy , Bone Marrow , Diagnosis , Lymphoma, Mantle-Cell , Prognosis , Survival RateABSTRACT
No abstract available.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Anemia, Aplastic/diagnosis , Bone Marrow/pathology , Diagnosis, Differential , Half-Life , Immunohistochemistry , Mutation , Myelodysplastic Syndromes/diagnosis , Retrospective Studies , Tumor Suppressor Protein p53/geneticsABSTRACT
In September 2011, the Korean Society of Hematology Lymphoma Working Party held a nationwide conference to establish a consensus for assessing bone marrow (BM) involvement in patients with lymphoma. At this conference, many clinicians, hematopathologists, and diagnostic hematologists discussed various topics for a uniform consensus in the evaluation process to determine whether the BM is involved. Now that the discussion has matured sufficiently to be published, we herein describe the consensus reached and limitations in current methods for assessing BM involvement in patients with lymphoma.
Subject(s)
Humans , Bone Marrow , Consensus , Hematology , LymphomaABSTRACT
BACKGROUND: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. METHODS: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. RESULTS: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. CONCLUSIONS: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Bone Marrow/metabolism , Cytarabine/therapeutic use , Daunorubicin , Karyotype , Leukemia, Myeloid, Acute/drug therapy , Mutation , Nuclear Proteins/genetics , Real-Time Polymerase Chain Reaction , Recurrence , Remission Induction , Retrospective Studies , Sequence Analysis, DNA , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
BACKGROUND: Coronary artery disease is an important cause of death in adults and stent insertion is one of the treatment modalities. The most severe adverse effect of a stent insertion is the formation of a thrombus; therefore, antiplatelet agents are used. The addition of cilostazol to low-dose aspirin and clopidogrel results in a better antiplatelet effect. However, laboratory tests to monitor the effect of cilostazol are insufficient. METHODS: We tested the inhibitory effect of cilostazol using maximal platelet aggregation in 20 healthy volunteers. Conditions for incubation and concentrations of cilostazol and prostaglandin E1 (PGE1) were established and aggregation was induced by 5'-adenosine diphosphate (ADP) and measured with light transmission aggregometry (LTA). Blood samples were incubated with 1 µM and 2 µM cilostazol for 10 minutes at room temperature, and 80 nM PGE1 was added and incubated for an additional 10 minutes. Aggregation was induced by ADP and reactivity was evaluated. RESULTS: The average maximum aggregation (MA) was 58.1% at 1 µM cilostazol and 22.0% when PGE1 was added. The average MA was 42.8% when cilostazol concentration was increased to 2 µM and 21.2% when PGE1 was added. Average inhibition of aggregation at 1 µM cilostazol was not statistically significant (P=0.085), but was significant (P=0.004) at 2 µM cilostazol. Aggregation was not inhibited even with 2 µM cilostazol and PGE1 in 2 volunteers, which suggests possible resistance to cilostazol. CONCLUSIONS: We designed a method to monitor the effect of cilostazol using in vitro incubation with PGE1.
Subject(s)
Adult , Humans , Adenosine Diphosphate , Alprostadil , Aspirin , Cause of Death , Coronary Artery Disease , Healthy Volunteers , In Vitro Techniques , Methods , Platelet Aggregation , Platelet Aggregation Inhibitors , Stents , Thrombosis , VolunteersABSTRACT
No abstract available.
Subject(s)
Humans , Chromosome Aberrations , Karyotype , Leukemia, Myeloid, Acute/diagnosis , Myelodysplastic Syndromes/complications , Myeloproliferative Disorders/complications , Philadelphia Chromosome , Survival RateABSTRACT
Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Calreticulin/genetics , Disease-Free Survival , Gene Frequency , Genetic Association Studies , Janus Kinase 2/genetics , Mutation/genetics , Primary Myelofibrosis/genetics , Receptors, Thrombopoietin/genetics , Republic of Korea , Thrombocythemia, Essential/geneticsABSTRACT
BACKGROUND: Efforts to overcome poor outcomes in patients with adult acute lymphoblastic leukemia (ALL) have focused on combining new therapeutic agents targeting immunophenotypic markers (IPMs) with classical cytotoxic agents; therefore, it is important to evaluate the clinical significance of IPMs. METHODS: Baseline characteristics and clinical outcomes of patients with adult ALL were retrospectively analyzed. The percentage of blasts expressing IPMs at diagnosis was measured by multicolor flow cytometry analysis. Samples in which > or =20% of blasts expressed an IPM were considered positive. RESULTS: Among the total patient population (N=230), almost all (92%) were in first or second hematological complete remission (HCR) and 54% received allogeneic hematopoietic cell transplant (allo-HCT). Five-year hematologic relapse-free survival (HRFS) and overall survival (OS) rates were 36% and 39%, respectively, and 45.6% and 80.5% of patients were positive for the IPMs CD20 and terminal deoxynucleotidyl transferase (TdT), respectively. Expression of CD20, CD13, CD34, and TdT was associated with HRFS rate, and expression of CD20 and CD13 was associated with OS rate, as was the performance of allo-HCT. In multivariate analysis, positivity for CD20 (HRFS: hazard ratio [HR], 2.21, P<0.001; OS: HR, 1.63, P=0.015) and negativity for TdT (HRFS: HR, 2.30, P=0.001) were both significantly associated with outcomes. When patients were categorized into three subgroups according to positivity for CD20 and TdT, there were significant differences in HRFS and OS among the subgroups. CONCLUSION: Positivity for CD20 and TdT expression and clinical risk group were prognostic factors in adult ALL.
Subject(s)
Adult , Humans , Cytotoxins , Diagnosis , DNA Nucleotidylexotransferase , Flow Cytometry , Multivariate Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Retrospective Studies , TransplantsABSTRACT
BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to recognize dysplastic changes and can also negatively affect the detection of cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53 immunoreactivity for discriminating between hMDS and AA and for estimating survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was performed by using the EnVision detection system (Dako, Denmark). We compared the results of IHC staining, BM findings, and chromosomal analyses, and determined overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells was higher among the patients with hMDS than among the patients with AA (P<0.001 and P=0.001, respectively). hMDS patients with increased CD34-positive cells had significantly poorer survival outcomes compared with those with normal number of CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB provide useful information for differentiating between hMDS and AA. CD34 IHC staining of BMC or BMB also provides useful information for estimating survival outcomes in hMDS patients.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Anemia, Aplastic/diagnosis , Antigens, CD34/metabolism , Bone Marrow/metabolism , Chromosome Aberrations , Diagnosis, Differential , Immunohistochemistry , Kaplan-Meier Estimate , Myelodysplastic Syndromes/diagnosis , ROC Curve , Tumor Suppressor Protein p53/metabolismABSTRACT
No abstract available.
Subject(s)
Humans , Male , Middle Aged , Antineoplastic Agents/adverse effects , Bone Marrow Cells/metabolism , Karyotyping , Leukemia, Myeloid, Acute/chemically induced , Leukemia, Promyelocytic, Acute/drug therapy , Oncogene Proteins, Fusion/genetics , Remission Induction , Tretinoin/therapeutic useABSTRACT
No abstract available.
Subject(s)
Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Ascitic Fluid/cytology , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Lymphatic Metastasis , Mutation , Neoplasm Staging , Quinazolines/therapeutic use , ErbB Receptors/genetics , Small Cell Lung Carcinoma/diagnosis , Tomography, X-Ray ComputedABSTRACT
No abstract available.
Subject(s)
Adult , Humans , Male , Middle Aged , Alleles , Fusion Proteins, bcr-abl/genetics , Heterozygote , Hydroxyurea/therapeutic use , Janus Kinase 2/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukocytes, Mononuclear/pathology , Leukocytosis/diagnosis , Mutation , Myeloproliferative Disorders/drug therapy , Phenotype , Splenomegaly/diagnosis , Thrombocytosis/diagnosis , Translocation, GeneticABSTRACT
No abstract available.
Subject(s)
Adolescent , Humans , Male , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Chromosome Deletion , Chromosomes, Human, Pair 7 , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl/genetics , Immunophenotyping , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: Therapy-related AML (t-AML) occurs as a late complication of chemotherapy administered to treat a prior disorder. Prognostic factors affecting the clinical outcome in t-AML have not yet been clearly defined; therefore, we evaluated these factors in this study. METHODS: Forty-eight patients diagnosed with t-AML within the past 10 years were enrolled, and their chemotherapy regimens categorized into 4 groups: alkylating agents (AK) only, topoisomerase II inhibitors (TI) and AK, TI only, and others. The prognostic factors affecting clinical outcome were evaluated. RESULTS: Five (10.4%), 21 (43.8%), 9 (18.8%), and 13 (27.0%) patients were treated with AK only, AK and TI, TI only, and others, respectively. Patients with an AML M3 phenotype showed significantly longer overall survival (OS; 55.1 vs. 14.3 months, P=0.040) and disease-free survival (DFS; 61.2 vs. 17.5 months, P=0.049) than other phenotypes. In contrast, patients with a complex karyotype showed significantly shorter OS (7.9 vs. 31.3 months, P=0.008) and DFS (9.5 vs. 38.6 months, P=0.046); additionally, patients with chromosome 5 or 7 abnormalities showed significantly shorter OS (9.1 vs. 30.7 months, P=0.011) than other phenotypes. Only the presence of a complex karyotype or AML M3 phenotype retained prognostic impact in a multivariate analysis. CONCLUSION: Only the AML M3 phenotype was identified as having a good prognosis, and this might suggest that it exhibits unique clinical features in t-AML patients. Moreover, our findings indicated that karyotype was the strongest prognostic indicator and predicted a poor prognosis for t-AML patients with a complex karyotype.
Subject(s)
Humans , Alkylating Agents , Chromosomes, Human, Pair 5 , Disease-Free Survival , Karyotype , Leukemia, Myeloid, Acute , Phenotype , Prognosis , Topoisomerase II InhibitorsABSTRACT
BACKGROUND: Fixation of cells is a critical procedure that can determine the success of immunocytochemical staining (ICC) of cytospin slides. In this study, we evaluated the efficacy of a number of fixatives to determine the ideal fixative for ICC of cytospin slides. METHODS: Sixteen patients with metastatic neoplasm in the body cavity were enrolled. Cytospin slides were prepared from each patient using 5 different fixatives (cold acetone, 95% ethanol, 1:1 methanol:ethanol, 3.7% formalin, and 3:1 methanol:acetone), and the suitability of each for use with Wright's stain was compared. For 4 of the samples, appropriate ICCs were performed using all 5 fixatives and the results were compared, while for 11 samples, only the first 3 fixatives were used for ICC. RESULTS: Using Wright stain, cold acetone, 95% ethanol, and 1:1 methanol:ethanol fixatives all showed similar efficacy when compared to the conventional methanol fixation method. However, the stain quality using 3.7% formalin or 3:1 methanol:acetone fixatives was poor due to deterioration of cell adhesion and distortion of cell morphology. Using ICC, cold acetone fixative showed stronger and more tumor-specific stainability than the 95% ethanol (decreased stainability in 6 stained slides, false positive staining of histiocytes/neutrophils in 4 stained slides, no staining of CD3 and terminal deoxynucleotidyl transferase [TdT]) and 1:1 methanol:ethanol fixatives (decreased stainability in 3 stained slides, false positive staining of histiocytes/neutrophils in 2 stained slides, no staining of CD3 and TdT). CONCLUSIONS: Cold acetone fixative was the most efficacious among the 5 fixatives tested in this study; therefore, it is the most appropriate fixative in the preparation of cytospin slides for ICC.
Subject(s)
Humans , Acetone , Cell Adhesion , Cold Temperature , DNA Nucleotidylexotransferase , Ethanol , Fixatives , Formaldehyde , Immunohistochemistry , MethanolABSTRACT
BACKGROUND: The prognostic impact of the presence of differentiating neuroblasts in bone marrow (BM) remains unclear in BM metastatic neuroblastoma (NB). We aimed to identify the prognostic impact of differentiating neuroblasts in BM at diagnosis and after chemotherapy. METHODS: A total of 51 patients diagnosed with BM metastatic NB at Asan Medical Center between January 1990 and July 2005 were enrolled. BM histology and laboratory data along with overall survival (OS) were compared with regard to the differentiation status of neuroblasts in BM at diagnosis and after chemotherapy. RESULTS: Among the 51 patients, 13 (25.5%) exhibited differentiating neuroblasts in BM at diagnosis and 17/51 (33.3%) exhibited them after chemotherapy. The only significant difference among patient groups was the improved OS in patients with differentiated neuroblasts in BM at diagnosis (P=0.021). In contrast, the differentiation status of neuroblasts in BM after chemotherapy did not affect OS (P=0.852). CONCLUSIONS: Our study is the first report describing the presence of differentiating neuroblasts in BM. The presence of differentiating neuroblasts in BM at diagnosis may be a favorable prognostic factor for patients with BM metastatic NB; however, the same phenomenon after chemotherapy is irrelevant to prognosis.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/pathology , Bone Marrow Cells/cytology , Bone Marrow Neoplasms/diagnosis , Cell Differentiation , Karyotyping , Neoplasm Grading , Neuroblastoma/diagnosis , Prognosis , Survival AnalysisABSTRACT
In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML.