Clinical Usefulness of Neutrophil-Lymphocyte Ratio as a Predictor of Henoch–Schönlein Nephritis

OBJECTIVE@#Henoch–Schönlein purpura is the most widespread systemic vasculitis during childhood. This study evaluated the relationship between neutrophil-lymphocyte ratio (NLR) and Henoch–Schönlein nephritis, which is important for the long-term prognosis of Henoch–Schönlein purpura.@*METHODS@#We retrospectively reviewed patients diagnosed with Henoch–Schönlein purpura at the Department of Pediatrics of Soonchunhyang University Bucheon Hospital between January 2007 and June 2018. One hundred and twelve patients under the age of 18 who were diagnosed with Henoch–Schönlein purpura according to Henoch–Schönlein purpura diagnostic criteria, European League Against Rheumatism were included in the study. Blood and urine test, gastroscopy and colonoscopy, and abdominal computed tomography performed during the first visit were included.@*RESULTS@#Among 112 Henoch–Schönlein purpura patients, 25 patients were Henoch–Schönlein nephritis. NLR was significantly increased in patients with Henoch–Schönlein nephritis compared to patients without nephritis (P=0.042), which is an independent predictor of Henoch–Schönlein nephritis.@*CONCLUSION@#This study showed that NLR could be a useful predictor of Henoch–Schönlein nephritis in patients with Henoch–Schönlein purpura.

Deferiprone Related Arthropathy in 11-Year-Old Boy with Hereditary Spherocytosis

Regular transfusion therapy in children with intractable hematologic disorder results in hemosiderosis. It causes several organ damages such as liver, heart, and endocrine system and increases risk of infection. Thus, iron-chelating therapy is essential to promote normal development, prevent excess iron overload and death in children. In abroad, deferiprone has been approved for use in thalassemic children with transfusion induced iron overload. Side effects associated with deferiprone include agranulocytosis, arthropathy, gastrointestinal symptoms, increased alanine aminotransferase levels, and zinc deficiency. Arthropathy has been reported to occur approximately 9%–38% of patients. We present an 11-year-old boy patient with hereditary spherocytosis, who experienced arthropathy while under deferiprone therapy.

Measles outbreaks in the Kyeongin area of the Republic of Korea, 2013-2014: A single-center experience in a country of measles elimination

OBJECTIVE@#To identify the source of infection and determine the clinical features and laboratory finding of measles infection.@*METHODS@#In 27 measles patients, except for 3 adult patients, the rest of 24 pediatric measles cases were analyzed with regard to age, sex, immunization status, transmission routes and molecular genotyping of measles virus. Eighteen measles patients who admitted in isolation ward were set apart to investigate clinical findings and its correlation with laboratory characteristics. Retrospective analysis of cases was conducted in this study.@*RESULTS@#Of the 24 pediatric patients, 23 (95.8%) had not received any measles-containing vaccine (MCV). Sixteen of the patients (66.7%) were aged <12 months. The suspicious index case of a girl aged 34 months was not vaccinated with MCV1 and got measles after a trip to Philippines, and molecular genotype was revealed as B3. Measles outbreaks in the community such as a restaurant were followed by this one imported case. According to analysis of 18 patients admitted in isolation ward, the median level of C-reactive protein (CRP) was 0.38 mg/dL and that of lactate dehydrogenase (LDH) was 1200 IU/L. All of the 18 patients had LDH levels above the normal range. Age correlated with CRP (ρ = 0.528, P = 0.024) and LDH (ρ = 0.501, P = 0.034). The duration of fever was correlated with the duration of fever before rash (ρ = 0.898, P < 0.01). The duration of hospitalization was correlated with CRP (ρ = 0.586, P = 0.011). The white blood cell counts were correlated with the levels of LDH (ρ = 0.505, P = 0.033), aspartate aminotransferase (ρ = 0.507, P = 0.032), and alanine aminotransferase (ρ = 0.481, P = 0.043).@*CONCLUSIONS@#Early weaning of maternally derived measles antibodies therefore vaccination of MCV1 at a young age from 9 months to 12 months should be considered in situations of early exposure. Furthermore, there is a call for consideration of scheduling an earlier age for the first dose of MMR vaccine in Europe. It is necessary for Korea to investigate the duration of the presence and quantitative analysis of maternal measles antibodies in infants and to reconsider the timing of MCV1.

Measles outbreaks in the Kyeongin area of the Republic of Korea, 2013–2014: A single-center experience in a country of measles elimination

Objective To identify the source of infection and determine the clinical features and laboratory finding of measles infection. Methods In 27 measles patients, except for 3 adult patients, the rest of 24 pediatric measles cases were analyzed with regard to age, sex, immunization status, transmission routes and molecular genotyping of measles virus. Eighteen measles patients who admitted in isolation ward were set apart to investigate clinical findings and its correlation with laboratory characteristics. Retrospective analysis of cases was conducted in this study. Results Of the 24 pediatric patients, 23 (95.8%) had not received any measles-containing vaccine (MCV). Sixteen of the patients (66.7%) were aged <12 months. The suspicious index case of a girl aged 34 months was not vaccinated with MCV1 and got measles after a trip to Philippines, and molecular genotype was revealed as B3. Measles outbreaks in the community such as a restaurant were followed by this one imported case. According to analysis of 18 patients admitted in isolation ward, the median level of C-reactive protein (CRP) was 0.38 mg/dL and that of lactate dehydrogenase (LDH) was 1200 IU/L. All of the 18 patients had LDH levels above the normal range. Age correlated with CRP (ρ = 0.528, P = 0.024) and LDH (ρ = 0.501, P = 0.034). The duration of fever was correlated with the duration of fever before rash (ρ = 0.898, P < 0.01). The duration of hospitalization was correlated with CRP (ρ = 0.586, P = 0.011). The white blood cell counts were correlated with the levels of LDH (ρ = 0.505, P = 0.033), aspartate aminotransferase (ρ = 0.507, P = 0.032), and alanine aminotransferase (ρ = 0.481, P = 0.043). Conclusions Early weaning of maternally derived measles antibodies therefore vaccination of MCV1 at a young age from 9 months to 12 months should be considered in situations of early exposure. Furthermore, there is a call for consideration of scheduling an earlier age for the first dose of MMR vaccine in Europe. It is necessary for Korea to investigate the duration of the presence and quantitative analysis of maternal measles antibodies in infants and to reconsider the timing of MCV1.

Rosai-Dorfman Disease of 4-Year-Old Girl

Rosai-Dorfman disease also known as sinus histiocytosis with massive lymphadenopathy is a benign, rare systemic disease characterized by a histiocyte proliferation which presents with lymphadenopathy. We report a case of a 4-year-old girl who presented with recurrent cervical lymphadenopathy with tenderness, without any other symptoms. After 1 month of medical treatment, her lymphadenopathy still remained, so we performed complete excision and biopsy. She was diagnosed on cytology as a case of Rosai-Dorfman disease. She responded well to become asymptomatic without recurrence by 1 month.

Case Report of Inferior Vena Cava Agenesis Accompanying Deep Vein Thrombosis / 임상소아혈액종양

A 17-year-old male patient was admitted to the author's hospital complaining of pain in both flanks. He had a history of being admitted to a tertiary-level hospital a year before, for swelling of the left limb. Deep vein thrombosis (DVT) was observed in the left common iliac vein, and the patient received anticoagulation therapy for six months. Prior to revisiting the hospital, he was symptom free and claimed to be healthy. An abdominal CT scan showed findings of congenital absence throughout the entire length of the IVC. To prevent the obstruction of the multiple collateral vessels developed around the IVC, and to improve the renal venous drainage, the patient was immediately started on with anticoagulation therapy. Reported herein is a case of an incidentally discovered congenital anomaly of the IVC in a patient with DVT.

Case Report of Inferior Vena Cava Agenesis Accompanying Deep Vein Thrombosis / 임상소아혈액종양

A 17-year-old male patient was admitted to the author's hospital complaining of pain in both flanks. He had a history of being admitted to a tertiary-level hospital a year before, for swelling of the left limb. Deep vein thrombosis (DVT) was observed in the left common iliac vein, and the patient received anticoagulation therapy for six months. Prior to revisiting the hospital, he was symptom free and claimed to be healthy. An abdominal CT scan showed findings of congenital absence throughout the entire length of the IVC. To prevent the obstruction of the multiple collateral vessels developed around the IVC, and to improve the renal venous drainage, the patient was immediately started on with anticoagulation therapy. Reported herein is a case of an incidentally discovered congenital anomaly of the IVC in a patient with DVT.

Comparison of Respiratory Morbidity in Late Preterm and Term Infants at a Single Institution

OBJECTIVE: This study was carried out to evaluate short-term respiratory morbidity in late preterm births compared with term births at a single center in Korea. METHODS: In retrospective study, we reviewed medical records of neonates that were born at Soonchunhyang University Bucheon Hospital from January 2002 to January 2011 and their mothers. The neonates were divided into two groups by their gestational age (GA): 535 late preterm births (GA, 34+0 to 36+6 weeks) and 3,037 term births (GA, 37+0 to 41+6 weeks). We compared late preterm births and term births in regard to maternal characteristics, neonatal characteristics, respiratory morbidities, and respiratory supports. RESULTS: Of 535 late preterm births, 117 (21.9%) had respiratory tract disease. Of 3,037 term births, 105 (3.5%) had respiratory tract disease. Compared term births, late preterm births had significantly more respiratory diseases such as apnea (odds ratio [OR], 37.3), respiratory distress syndrome (OR, 34.0), transient tachypnea of newborn (OR, 5.9), and pneumonia (OR, 2.2). Duration of oxygen supply was longer in term than in preterm births. Oxygen supply through isolette and use of surfactant were more frequent in late preterm than term births. It was not differ from two groups to use continuous positive airway pressure and mechanical ventilation. CONCLUSION: This study showed that late preterm births had significantly higher respiratory morbidity than term births. Therefore, we should have more attention to evaluate and manage when late preterm birth occur than before. Also it is necessary to study long-term respiratory outcomes of late preterm births and discuss about perinatal care system.

A Clinical Study of Lobar/Lobular Pneumonia in Children / 소아알레르기및호흡기학회지

PURPOSE: We aimed to evaluate the clinical characteristics and etiological organisms associated with lobar/lobular pneumonia in Korean children. METHODS: Children hospitalized due to radiographically confirmed lobar/lobular pneumonia were evaluated prospectively between June 2006 and May 2008. Anti-Mycoplasma pneumoniae IgM/IgG (at admission and follow-up), blood cultures, throat swabs for bacterial detection or sputum culture, respiratory viruses (Respiratory syncytial virus, Adenovirus and Influenza A/B) antigen testing, and urinary antigen testing for S. pneumoniae were performed. RESULTS: Two hundred eighty-eight immunocompetent children (mean age, 5.9 years) were enrolled. The age distribution showed a peak frequency at 2-6 years of age (<2 years, 8.7%; 2-6 years, 60.8%; 7-10 years, 22.6%; 11-15 years, 8.0%). Typical respiratory organisms were identified in 64.9% of cases. Identified organisms were Mycoplasma pneumoniae (50.7%), bacteria in (5.9%), viruses (2.1%) and mixed infection (5.9%). Mycoplasma pneumoniae was the most commonly identified organism in all age groups. The majority (88.9%) of bacterial pneumonias including mixed infection were caused by Streptococcus pneumoniae. Mycoplasma pneumonia was the most frequent at 5-6 years of age, but bacterial pneumonia was most frequent at 1-2 years of age. Lobar/lobular pneumonia began to increase from August and showed peak incidence in November and December. The levels of WBC, ESR, and CRP more significantly elevated in those with bacterial pneumonia than in children with mycoplasma pneumonia. Pleural effusion was present in 18.1% of cases. In these cases, the duration of fever and hospitalization was prolonged, and the ESR and CRP levels were significantly higher, than those without pleural effusion. CONCLUSION: Mycoplasma pneumoniae was the most common organism causing lobar/lobular pneumonia in children. Mycoplasma pneumoniae was the most frequent causative organism at 5-6 years of age. On the other hand, bacterial pneumonia was more common at 1-2 years of age. Thus, age may be a significant factor for the diagnosis and treatment of lobar/lobular pneumonia in children.

Cytogenetic and Molecular Diagnosis in Childhood Cancer / 소아과

No abstract available.

Epidemiology and Clinical Outcomes in Children with Aplastic Anemia in Korea: Retrospective Study / 대한소아혈액종양학회지

PURPOSE: The annual incidence of aplastic anemia (AA) in Asian countries is higher than in Western countries. The pathogenesis in AA has been investigated in hematopoiesis and immunology. Recently, the survival rate and the quality of life of the patients with AA have been steadily improved by the development of a variety of treatments such as the immunosuppressive therapy (IST), and hematopoietic stem cell transplantation (HSCT). The Korean Society of Pediatric Hematology-oncology retrospectively investigated the incidence, treatment strategies, survival rate, and time to become independent from transfusion in patients with AA, who were diagnosed from January 1st, 1991 to December 31st, 2000 in Korea. METHODS: All the questionnaires were sent to a group of training hospitals, and we collected about 600 questionnaire forms from 27 hospitals. However, 493 reports were available for data analysis. RESULTS: The male and female ratio in AA is 1.1 (259 males vs. 234 female). The median age at diagnosis is 9 years old (range; 0.8~16 years old). The annual incidence of children with AA in Korea is 4.5 per million on the basis of Korean pediatric population. In etiology, there are 20 cases (4.1%) in congenital and others in acquired AA. In acquired AA, the cause of illness was not identifiable for most of the patients, but 1 patient had hepatitis-associated AA, and 3 patients developed the illness after medication. According to the initial laboratory data at diagnosis, the peripheral blood findings showed that hemoglobin is 7.1+/-2.4 g/dL, white blood cell 3, 200/microL (200~16, 550), absolute neutrophil counts 670/microL (0~12, 487), platelets 19, 000/microL (1, 000~500, 000), and corrected reticulocytes 0.18% (0.0~4.7). The bone marrow examination revealed that cellularity was below 25% in 348 patients, and over 25% in 105 patients. In the available data, 269 patients (54.6%) were diagnosed of severe aplastic anemia (SAA) and 224 patients of non-SAA (NSAA). HSCT were done for 96 patients (19.5%) and others received another treatments such as the IST. The anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) treatment was done for 263 cases, corticosteroids for 259, cyclosporine A (CSA) for 215, and anabolic steroids for 138. The combination IST including ATG or ALG plus corticosteroid plus CSA were applied to 154 children with AA, and transfusion only in 37, as conservative care. In case of those patients with HSCT, the time from diagnosis to transplantation was 12 months (1~144 months) and the sources of stem cells were bone marrow in 82 cases, growth factor mobilized peripheral blood in five, and cord blood in six. There were 57 patients transfused below 40 units of blood products before HSC transplantation. Graft rejection was identified from 16 patients, and booster transplantations were done for 12 patients among them. In complications of HSCT, the graft versus host disease was developed in 20 patients and viral diseases in 12 cases including the CMV, herpetic infection, and hepatitis. Also, one patient suffered from veno-occlusive disease. The overall survival rate in children with AA is 64.3%. The survival rate in HSCT is better than that IST (76.9% vs. 62.6%, P< 0.05). In IST, overall survival rate in very SAA showed lower than SAA and NSAA, and in SAA lower than NSAA in case of absolute neutrophil count below 200/microL (P< 0.05). There was no significant difference in terms of the sex, age at beginning of treatment. In HSCT, transfusion was not related to the survival rate. However, overall survival rate is better in short interval between diagnosis and HSCT than in long interval (P< 0.05). There was no significant difference in the probability of transfusion independence according to treatment strategies, even though it was 71.0% in HSCT and 12.8% in immunosuppressive therapy at the end point of survey (P=0.47). The response pattern was as follows. There were 155 cases of complete response, 110 of partial response and 120 of no response in spite of various treatments. The relapse after treatment was found in 11 patients after IST, of which 6 patients experienced more than 2nd relapse. The median time between the end of treatment and relapse was 16 months (6~84 months). Only three cases developed into other diseases (1 case into acute myeloid leukemia and 2 cases into myelodysplastic syndrome). The median time from diagnosis to the end of treatment was 62 months (0.5~174 months). In fatal cases, the median time between diagnosis and death was 29 months (0~144 months) despite several therapeutic strategies. CONCLUSION: In Korea, the annual incidence of children with AA is 4.5 per million. This result is similar to the ones reported in other Asian countries, but higher than those in Western countries. Although a lot of children with AA received various therapies including IST or HSCT, new treatment strategies have to be developed to improve the survival rate and the quality of life of children with AA

Epidemiology and Clinical Outcomes of Childhood Wilms Tumor in Korea / 대한소아혈액종양학회지

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed, The differences between groups were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.

Arsenic Trioxide (As2O3) Induced Apoptosis in NB4 Cell lines / 대한혈액학회지

BACKGROUND: Recently, inorganic arsenic trioxide (As2O3) was reported to induce complete remission in a high proportion of patients with refractory acute promyelocytic leukemia (APL). To illustrate cellular and molecular mechanisms of As2O3 in the treatment of APL, many experimental studies were performed on APL-derived cell lines in vitro. Previous studies showed that As2O3 inhibited proliferation and induced apoptosis in the APL-derived cell lines. This study was done to clarify the in vitro mechanisms of As2O3-induced apoptosis in APL-derived NB4 cell lines. METHODS: To determine the effects of As2O3 in the various concentrations, NB4 cells were cultured with 0.1 to 2micro M/L of As2O3. To assay the apoptosis in NB4 cell lines, DNA fragmentation assay and TUNEL were performed. To find out the molecular change of As2O3- induced apoptotic NB4 cell lines, RT-PCR and Western blot analysis for PML-RARalpha chimeric protein expression and flow cytometry for bcl- 2/bax expression were performed. To clarify the caspase activation pathway, Western blot analysis and flow cytometry for procaspase expression were performed. RESULTS: As2O3 induces apoptosis on NB4 cells in relatively high concentration (0.5 to 2 micro M/L) for 2 days. After 2 days of culture the PML-RARalpha chimeric protein expression decreased rapidly by Western blot and RT-PCR analysis and bcl-2 expression also decreased by flow cytometry. The expression of bax by flow cytometry showed a marked increase in high concentration (2micro M/L) but there was no change in low concentration (0.5micro M/L). In the Western blot analysis, the amount of pro`enzyme of caspase-3 was significantly decreased in the cells with high concentration (2micro M/L) compared with that in the cells with low concentration (0.5micro M/L). As2O3 induces proteolytic processing of pro-caspase 7 but not pro-caspase 9 and 8. CONCLUSION: Apoptosis of APL-derived NB4 cell lines was induced by As2O3 and progressed rapidly in higher concentrations. During apoptosis, activation of caspase-7 pathway and degradation of PML-RARalpha chimeric protein, decrease in bcl-2 and increase in bax were shown.

Epidemiology and Clinical Characteristics of Childhood Acute Lymphoblastic Leukemia in Korea / 대한소아혈액종양학회지

PURPOSE: Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of all cases of childhood leukemia. We investigated epidemiology, clinical and laboratory features and treatment outcome of the children with ALL in Korea during recent 5 years. METHODS: One thousand forty nine patients were enrolled between January 1994 and December 1998 from 37 major hospitals in Korea. The data regarding the clinical and laboratory features including age, WBC counts at diagnosis, immunophenotype, morphology, cytogenetics and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed. The differences between groups analyzed by log-rank test. RESULTS: There were 597 males and 452 females. The distribution between the age 2 and 5 years is most common in 46.1%. The annual incidence rate per 100,000 population varied from 1.6 to 2.2. The 5 year event free survival (EFS) rates according to good prognostic factors were as follows: 67% bet ween 1-9 year of age at diagnosis, 69% in under 10,000/mm3of initial WBC count, 74% in early pre-B cell CALLA ( ) immunophenotype, 65% in L3 morphology, 68% in no CNS invasion. Most of patients were treated by CCG treatment protocol. The 5 year EFS was 63%. Main complications were sepsis (21.8%) and hemorrhage (12.5%). The relapse rate was 15.6%. The common causes of death were sepsis, DIC, pneumonia, relapse. CONCLUSION: Our results could provide the most recent and important information about acute lymphoblastic leukemia of children in Korea.

Determination of Sensitivity of RT-PCR for Cyokeratin 19 and Detection of Micrometastasis from Bone Marrow of Breast Cancer Patients

BACKGROUND: The detection of micrometastatic cells in patients with breast cancer may aid in determining of prognosis and in developing new therapeutic approaches. In this study, we evaluate an assay to identify breast cancer cells in the bone marrow of patients with breast cancer by using reverse-transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (CK-19) transcripts. METHODS: A CK-19 specific-nested RT-PCR assay was developed and optimized by using limited dilutions of an MCF-7 breast-cancer cell line mixed with normal bone-marrow specimens. The optimized assay was then used to examine bone-marrow samples obtained from 60 patients with breast cancer. The specificity was assessed by examining 20 negative controls using malignant hematologic disease. RESULTS: In the sensitivity calibration system, CK-19 expressing tumor cells were detected in the mixture of 10 MCF-7 cells in 107 normal bone-marrow cells. All 20 neagtive control samples failed to amplify. Bone marrow samples from 10 of 60 patients (16.7%) with breast cancer scored positive, indicating micrometastasis of the bone marrow. Seven of the 37 samples from patients whose axillary lymph nodes were negative based on conventional histopathological studies were positive when the CK-19 RT-PCR method was used. CONCLUSION: RT-PCR for CK-19 is a sensitive, specific, and rapid method for detecting micrometastatic mammary carcinoma cells in the bone marrow of patients with breast cancer. It could be helpful in diagnosing and monitoring metastastic breast cancer and detecting of micrometastasis. This method should be evaluated using a larger number of patients for long-term follow-up.

Use of RT-PCR for Cytokeratin 19 to Detect Micrometastases in Bone Marrow of Follow-up Patients with Breast Cancer after Surgery

PURPOSE: We have previously reported that the reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK 19) is a highly sensitive and specific method for detecting micrometas tases in the bone marrow of patients with primary breast cancer. Thus, we conducted this study to identify occult metastatic cells in the bone marrow of follow-up patients with breast cancer by using the RT-PCR for cytokeratin 19 after surgery. METHODS: We studied 42 patients with breast cancer who had no evidence of relapse, 3 patients who had a local relapse, and 7 patients who had distant metastases. Bone-marrow aspirates were taken from the single posterior iliac crest under local anesthesia anesthesia at a median of 45 months after surgery. RT-PCR for CK19 was done by using two 30-cycle rounds with nested primers. RESULTS: Occult metastases were found in 23% of the 52 breast-cancer patients. None of the bone-marrow aspirates showed any evidence of tumor involvement by using conventional cytology. RT- PCR was positive for CK 19 in 19% of the 42 patients without relapse, and in 40% of the 10 patients with local or distant relapse. CONCLUSION: RT-PCR for CK 19 is a sensitive method for detecting tumor cells in the bone marrow of follow-up patients with breast cancer after surgery. This assay may be useful in detecting metastastic disease, as well as in monitoring the effectiveness of systemic therapy. However, a large study with long-term follow-up is required in order to clarify its clinical significance and usefulness.

Clinical Significance of bcl-2 and p53 protein Expression in Patients with Malignant Lymphoma / 대한혈액학회지

BACKGROUND: Overexpression of bcl-2 protein is observed both in follicular lymphoma, in which bcl-2 has usually undergone a translocation t (14;18). The experimental findings that transfection of bcl-2 in to murine lymphoid cells confers resistance to nitrogen mustard and camptothecin by inhibiting apoptosis suggests that bcl-2 overexpression may confer clinical drug resistance in lymphomas. In contrast to bcl-2, p53 arrests cells exposed to DNA-damaging agents in G1 to allow DNA repair or if essential repairs are not possible, promotes apoptosis. Experimentally, loss of p53 function produces cellular resistance to alkylating and topoisomerase-II drug classes, suggesting that loss of p53 function in lymphomas may cause drug resistance. These observations led to the hypothesis that bcl-2 and p53 play a role in the development of drug resistance in lymphoma. Although several studies assessed the association between bcl-2 expression and disease-free survival, they reached conflicting conclusions. METHODS: We analyzed tumor tissue from 42 patients with advanced NHL for p53 and bcl-2 expression and correlation with multiple clinical characteristics, response to therapy and overall survival. Among 42 tumors, 8 (19.0%) tumors had bcl-2 expression and 19 (45.2%) had a p53 overexpression. RESULTS: A significant correlation was found between bcl-2 expression and poor performance, advanced stage (stage III and IV) at diagnosis, and bone marrow involvement in a univariate analysis (P50%) were more likely to be poor prognosis than tumors with negative or week expression (<50%) and to have a shorter long-term survival (28.6% vs 75.5%; P<0.05). However, the expression of p53 did not correlate with any clinical characteristics and overall survival was not influenced by p53 protein expression. CONCLUSION: These results suggest that bcl-2 protein expression in patients with malignant lymphoma appears to be predictive of shorter long-term survival and it might be considered as a strong independent prognostic factor.

Telomerase Activity in HL-60 Cells After Treatment with Differentiating Agents / 대한혈액학회지

BACKGROUND: Telomeres are repetitive DNA fragments at the termini of chromosomes functioning as stabilizing elements of the DNA. A ribonucleoprotein polymerase, called telomerase, is responsible for the synthesis of such telomeric repeats in embryo and germ cells. During ontogenesis of most normal human somatic cells, there exists a physiological telomerase repressing mechanism. In contrast, malignant cells are characterized by an unlimited progressive potential. Certain physiological agents, such as all-trans retinoic acid (ATRA), 13-cis retinoic acid (13-cisRA), 1alpha-25 dihydroxy vitamin D3 (VD3) and cytosine arabinoside (Ara-C), promote further differentiation of leukemic cells into mature granulocytes and monocytes and subsequently undergo apoptosis. METHODS: To determine if a potential linkage is present between telomerase regulation and the differentiation of malignant hematopoietic cells, the changes in telomerase activity during the maturation of HL-60 cells induced by ATRA, 13-cisRA, VD3 and Ara-C were investigated. RESULTS: Differentiating agents induce HL-60 cells to differentiate into CD11b+ granulocytes and monocyte/macrophages, respectively. Approximately 98% of HL-60 cells acquired the expression of CD11b+ antigen after ATRA, 13-cisRA or Ara-C treatment for 5 days. After 1 day treatment with differentiating agents, no significant difference in telomerase activity was shown between untreated and treated HL-60 cells. A dramatic inhibition of telomerase activity occurred at 3 days treatment of ATRA compared to untreated HL-60 cells. Longer treatment for 5 days with differentiating agents resulted in further decrease of telomerase activity. However, telomerase activity in HL-60 cells was decreased slightly by the VD3 or Ara-C treatment, even though for 5 days. No evidence of differentiation and slight decrease of telomerase activity were observed in ATRA-treated K-562 cells for 5 days. These decrease of telomerase activity were dependent on the incubation time and dose. CONCLUSION: These data clearly show the role of telomerase activity during the differentiation of HL-60 cells. This in vitro model can be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.

The Expression of Fas Antigen and Apoptosis in Patients with Myelodysplastic Syndromes and Its Clinical Relevance / 대한혈액학회지

BACKGROUND: The myelodysplastic syndromes (MDS) are a group of acquired clonal hematopoietic disorders characterized by the peripheral cytopenias and hypercellular or normocellular dysplastic bone marrow. The event responsible for the development of MDS is generally not known. Several recent reports have described an increased frequency of apoptosis in bone marrow cells from patients with aplastic anemia or MDS. Gersuk et al observed that Fas ligand expression was significantly increased on bone marrow cells from MDS patients as compared to normal individuals. METHODS: We examined apoptosis and Fas antigen expression using ISNEL method and immunohistochemistry on marrow cells from 36 patients with MDS. RESULTS: Among the 36 patients, 15 patients (42%) demonstrated apoptosis positive cells (>15%) and 9 patients (25%) demonstrated positive Fas antigen expression (>20%). The presence of apoptosis significantly correlated with hemoglobin level at diagnosis (P<0.05) and the expression of Fas antigen significantly correlated with bone marrow cellularity and CD34 positive cell aggregate group at diagnosis (P<0.05). There was no statistically significant relationship between apoptosis and Fas antigen expression. The median survival of all patients with MDS was 44 months (2-117+). Multivariate analysis showed that FAB classification and hemoglobin level at diagnosis were significant prognostic factor but presence of apoptosis and expression of Fas antigen had no significance. CONCLUSION: The data indicate that the apoptosis and expression of Fas antigen are present in patients with MDS and correlate with some clinical parameters but not significantly associated with survival period of the patients with MDS.

Detection of Minimal Residual Diseases in Childhood Leukemias

No abstract available.