Development of acute myocardial infarction in a young female patient with essential thrombocythemia treated with anagrelide: a case report / 대한혈액학회지

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder with a prolonged clinical course. Since this disorder is considered to be at increased risk of thromboembolism, therapy is mainly focused on the decreased risk of thrombohemorrhagic events by use of cytotoxic agents. Anagrelide is a phosphodiesterase III inhibitor which is utilized in the treatment of ET for the reduction of platelets. However, patients treated with anagrelide might experience cardiovascular adverse effects including myocardial infarction (MI), although these events are rare. Herein, we report a case of a 30-year-old female with well controlled ET by anagrelide, who eventually developed an acute non-ST elevation myocardial infarction (MI). There has no found any cardiovascular risk factors in this ET patient, strongly suggesting that anagrelide might be the cause of MI. Therefore, cardiovascular function should be monitored in those patients prescribed with anagrelide.

A Case of Kikuchi Fujimoto's Disease Accompanied by Hemophagocytic Lymphohistiocytosis / 대한혈액학회지

Kikuchi's disease and hemophagocytic lymphohistiocytosis (HLH) present different clinical characteristics, especially in prognosis, although both diseases have the clinical similarity in initial presentations. Kikuchi's disease usually has a self-limiting clinical course, but HLH can be fatal. Accordingly, it is important that the differential diagnoses and decision as to initial treatment be made as soon as possible, at the time of clinical presentation. In the case of Kikuchi's disease accompanied with HLH, the decision concerning initial treatment can be very difficult, because these cases have been rarely reported and the prognosis is unpredictable. We report a case of a 21-year-old female diagnosed with Kikuchi's disease accompanied with HLH. Treatment involved steroid therapy, as for treatment of HLH. Recovery was complete. Kikuchi's disease with HLH can be completely treated with more aggressive therapy than used for Kikuchi's disease alone.

Mutation of the N-ras Gene in a Patient Suffering from the Blast Phase of Chronic Myelogenous Leukemia / 대한혈액학회지

The blast phase in chronic myelogenous leukemia (CML) is associated with mutation of several genes. It is well known that p53 gene mutation plays a key role in the myeloid or lymphoid blast phase of CML. But for the case of the N-ras gene, the association between N-ras mutations and the blast phase of CML is not yet known. We report here on a case of detecting N-ras point mutation without p53 mutation in a 64 year-old man who suffered from the lymphoblastic blast phase of CML.

T-cell Large Granular Lymphocytic Leukemia: A Case Report / 대한혈액학회지

T cell large granular lymphocytic leukemia (T-LGL leukemia) is defined as a clonal proliferative disorder of CD3+ cytotoxic T cells. T-LGL leukemia usually expresses CD3+, CD4-, CD8+, CD16+, CD56- and CD57+ cell markers, and this represents a rearrangement of the T cell receptor (TCR) gene. The clinical course is indolent in most cases, but on rare occasions, when CD3+ and CD56+ are expressed on the leukemic cells, it can be more aggressive. We experienced a patient with T-LGL leukemia and the disease was indolent at the time of diagnosis, and so any specific treatment was not required. Two years after the initial diagnosis, her clinical course became quite aggressive as the CD 56+ cell surface antigen was expressed. We report here on the first case of T-LGL leukemia in Korea and we review the relevant literature.

Abrogation of U266 Multiple Myeloma Cell Proliferation Via Inhibition of NF-kappaB Activation by Curcumin / 대한혈액학회지

BACKGROUND: Curcumin is a naturally occurring biologically active compound, and it has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. It is known for its anti-proliferative and proapoptotic effects in several cancer cells. Curcumin's effects on the mechanisms of cell survival and the expression of various cytokines were investigated in U266 cells and the in vivo effects of curcumin were examined using an animal model. METHODS: Cell proliferation assay and flow cytometry were used to examine cell proliferation, along with cell cycle analysis. The protein expressions were analyzed by Western blotting and the expressed levels of cytokines were analyzed by the ELISA method. RESULTS: Curcumin inhibited U266 cell growth in a dose-dependent and time-dependent manner. Cell cycle analysis showed an increased sub-G1 phase, a down regulated cyclinD1 expression and an induced p21 expression. Apoptosis induced a down regulated procaspase 3 expression and it induced cleaved PARP. Curcumin inhibited the IL (interleukin)-6 induced cell signal pathway via decreasing the STAT1 an 3, Erk cyclinD1 and c-myc expressions. Also, administration of 25mg/kg curcumin to a U266 animal model inhibited cancer cell engraftment in the bone marrow and it decreased the IL-6, sIL-6R and IL-8 expression levels. CONCLUSION: Curcumin induced cell cycle arrest and apoptosis and it inhibited the IL-6 mediated signal transduction pathways in U266 cells. Similar to the in vitro results, curcumin inhibited cancer cell proliferation and the expression of cytokine in vivo.

Correlation of Vascular Endothelial Growth Factor-D Expression and VEGFR-3-Positive Vessel Density with Lymph Node Metastasis in Gastric Carcinoma

Lymph node metastasis is an important prognostic factor in gastric cancer. Vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that activates VEGF receptor (VEGFR)-3, a receptor expressed in the lymphatic endothelium. We investigated the clinical value of VEGF-D expression and VEGFR-3 positive vessel density in gastric carcinoma with regard to lymphangiogenesis. Immunohistochemical staining was used to determine the expression of VEGF-D and VEGFR- 3 in specimens from 104 cases of resected gastric cancer. VEGF-D expression was observed in 62.5% of the gastric cancers and in 9.6% of the non-neoplastic gastric tissue. The VEGFR-3-positive vessel density was significantly greater in the VEGFD positive group than the negative group. VEGF-D expression was significantly associated with lymph node metastasis, increased serum CEA levels, and the nonsignet ring cell type. The VEGFR-3-positive vessel density was correlated with tumor size, lymphatic invasion, and lymph node metastasis. The VEGF-D expression and high VEGFR-3-positive vessel density were significant poor prognostic factors for relapse-free survival. These results suggest that VEGF-D and VEGFR-3-positive vessel density are potential molecular markers that predict lymphatic involvement in gastric carcinoma.

Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog

Nanog, a homeodomain (HD) transcription factor, plays a critical role in the maintenance of embryonic stem (ES) cell self-renewal. Here, we report the identification of an alternatively-spliced variant of nanog. This variant lacked a stretch of amino acids (residues 168-183) located between the HD and tryptophan-repeat (WR) of the previously-reported full length sequence, suggesting that the deleted sequence functions as a linker and possibly affects the flexibility of the C-terminal transactivation domain relative to the DNA binding domain. Expression of mRNA encoding the splice variant, designated as nanog-delta 48, was much lower than that of the full length version in human ES cells. The ratio of nanog-delta 48 transcript to full length transcript increased, however, in multipotent adult progenitor cells. EMSA analysis revealed that both forms of Nanog were able to bind a nanog binding sequence with roughly the same affinity. A reporter plasmid assay also showed that both variants of nanog modestly repressed transactivation of gata-4, whose expression is proposed to be inhibited by nanog, with comparable potency. We conclude that, despite the difference in primary structure and expression pattern in various stem cells, the alternatively-spliced variant of Nanog has similar activity to that of the full length version.

A Case of Severe Chronic Active Epstein-Barr Virus Infection with T-cell lymphoproliferative Disorder

Chronic infection with Epstein-Barr virus (EBV) without previous immunodeficiency or immuno-suppressive therapy is relatively rare. Severe chronic active EBV (SCAEBV) infection was reported for the first time in 1984 as 'chronic mononucleosis syndrome', and diagnostic criteria were proposed. It is characterized by clinical features including fever, severe hepatosplenomegaly, lymphadenopathy, hematologic features such as anemia and thrombocytopenia, and elevated antibody titers to EBV. We experienced a 21-year-old woman who initially presented with fever and chronic fatigue; however, no definite diagnosis could be made at the time of admission. Three months after the initial admission, there was evidence of only splenomegaly and the patient had persistent, multiple, paraaortic lymphadenopathies in abdominal CT. Diagnostic splenectomy was performed, and SCAEBV infection with T-cell lymphoproliferative disorder was ultimately diagnosed.

A Case of Primary Adrenal Gland Lymphoma

Primary adrenal lymphoma is extremely rare. We describe a case of non-Hodgkin's lymphoma of diffuse large B-cell type with right adrenal involvement. The patient received chemotherapy and external irradiation and achieved complete remission of the disease. We describe the case of primary adrenal lymphoma with a review of the literature on this unusual neoplasm. Primary adrenal lymphoma should be included in the differential diagnosis of adrenal mass.

A Case of Henoch-Schonlein Purpura with Portal Vein and Mesenteric Vein Thrombosis / 대한혈액학회지

Henoch-Schonlein purpura is an immunologically mediated systemic leukocytoclastic vasculitis of small vessels that is characterized by symmetric nontraumatic, nonthrombocytopenic, painless palpable purpura on the lower extremities and buttock, arthralgias on usually the knees and ankles, gastrointestinal symptoms and glomerulonephritis. Although the jejunum and ileum are most frequently affected, any portion of gastrointestinal tracts may be involved. Generally, gastrointestinal manifestations of Henoch-Schonlein purpura are the edematous wall of involved bowel, submucosal hemorrhage and erosion. We experienced a 56-year-old man with Henoch-Schonlein purpura who initially presented acute abdominal pain with portal vein and superior mesenteric vein thrombosis.

Induction of Cytotoxic T Lymphocytes by Dendritic Cells Pulsed with Murine Leukemic Cell RNA / 대한혈액학회지

BACKGROUND: This study was done to assess the feasibility of dendritic cell generation from murine bone marrow and the efficacy of dendritic cells pulsed with total RNA to induce specific cytotoxic T lymphocyte response against leukemic cells. METHODS: Nucleated cells of inbred BALB/c mice were obtained and cultured with granulocyte/macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) to induce dendritic cells. Total RNA of WEHI-3BD+, a myelomonocytic leukemia cell line from BALB/c, was transfected into the dendritic cells using liposome. RNA pulsed dendritic cells were irradiated and administered to the BALB/c mice intraperitoneally and splenic T lymphocytes were harvested. After restimulation with leukemic cells, T cell proliferation and specific cytotoxicity was assessed. RESULTS: Cells cultured with GM-CSF and lipopolysaccaride were found to have prominent dendritic processes. The percentage of cells showing high expression of both MHC class II and CD80, CD86, or CD11c was 69.6 %, 63.7%, and 41.8%, respectively. T cells stimulated by WEHI-3BD+ total RNA pulsed dendritic cells using DOTAP showed enhanced proliferation than those stimulated by total RNA or media only (P=0.05). When T cells were cocultured with WEHI-3BD+ as target cells, T cells stimulated by WEHI-3BD+ total RNA pulsed dendritic cells using DOTAP showed much increased cytotoxicity than controls. CONCLUSION: Dendritic cells pulsed with total leukemic RNA could stimulate T cells to induce specific cytotoxic effect.

Radiofrequency Thermal Ablation of Metastatic Liver Tumors: Usefulness of Combined Chemotherapy

PURPOSE: To assess the usefulness of radiofrequency (RF) thermal ablation with combined chemotherapy for the treatment of metastatic liver tumors. MATERIALS AND METHODS: A non-randomized, comparative study was performed in 21 patients with metastatic liver tumors. Inclusion criteria were that these should be less than five in number and less than 6 cm in diameter. Two groups were designed for comparison of the local and remote (new intrahepatic or extrahepatic) tumor control rate (Group A: RF alone, n=11; Group B: RF+combined chemotherapy, n=10). There was no significant difference in age, sex, and mass size between the two groups (p>0.05). All ablations were performed percutaneously with a 50W RF generator and 15G-needle electrode (RITA Medical System Inc.) under US guidance. In group B, six cycles of systemic chemotherapy were performed every month immediately after RF ablation. Follow-up CT scans were obtained within 24 hours of ablation and were compared with the findings of pre-ablation CT scanning. If an ablated lesion covered the mass without any residual enhancing foci, this was defined as complete ablation. Three and six months after ablation, local and remote tumor control rates were compared between the two groups (follow up: range 4 -17 (mean, 10.2) months. RESULTS: In group A, the local tumor control rate was 43.8% (7/16) and 31.2% (5/16) at 3 and 6 months follow-up, respectively, while in group B, the corresponding rates were both 75% (15/20). At three months, the difference in this rate between the two groups was not significantly different (p>0.05), but at 6 months there was significant difference (p<0.05). At 6 months follow-up, the remote tumor control rate for Group A and Group B was 27.3% (3/11) and 80.0% (8/10), respectively, reflecting a significant difference between the two groups (p<0.05). CONCLUSION: In patients with metastatic liver tumor, radiofrequency thermal ablation with combined chemotherapy may be superior to RF thermal ablation alone for both local and remote tumor control.

A Case of Acute Promyelocytic Leukemia with 46, XX, del(5)(q23)/47, XX, del(5)(q23), +8 but Without (15;17) Translocation / 대한혈액학회지

Acute promyelocytic leukemia (APL/AML- M3) is a distinct subtype of acute myelogenous leukemia, which is characterized by unique morphologic, cytogenetic, molecular, and clinical features. In almost all APL patients, a characteristic t(15;17)(q22;q21) is found, resulting from the fusion of the PML gene and retinoic acid receptor alpha (RAR ) gene. This chromosomal translocation in APL may present variant translocations, and may be associated with secondary chromosomal abnormalities. The most frequent accompanying karyotypic aberration is trisomy 8 in APL. We are reporting a case of a 17-year-old woman who was diagnosed with APL. Cytogenetic study revealed that 46, XX, del(5)(q23)/47, XX, del(5)(q23), +8 chromosomal abnormality but without t(15;17). However, the presence of PML/RAR chimera was found with reverse transcriptase PCR. It is well known that the association of trisomy 8 on top of t(15;17) in APL cases. However, in our review, the mosaicism of del(5)(q23) with trisomy 8 in APL might be the first case. Whether this patient will behave the typical APL cases having good prognosis or not will be interesting to see.

Mutation of The p53 Gene in Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: A p53 gene is one of the member of tumor suppressor genes involved in the control of cell cycle. The alteration of the p53 gene induces uncontrolled cellular proliferation leading to the development of tumor. Mutations of the p53 gene were found in various human cancers including hematologic malignancies. The incidence of the p53 mutation in acute myelogenous leukemia was reported to be relatively low, however, there has been no report as to the incidence and the characteristics of the p53 mutation in acute myelogenous leukemia in Korea. METHODS: Polymerase chain reaction and single strand conformational polymorphism(PCR-SSCP) was done to screen abnormal band shifts in exons 5, 6, 7, 8 of p53 gene in myeloid blasts obtained from bone marrow aspirates at the time of diagnosis from patients with de novo acute myelogenous leukemia. Mutation of the p53 gene was confirmed by direct sequencing with Sanger method in the DNAs with abnormal band shifts. Cytogenetic analysis of the bone marrow was performed by G-banding method. RESULTS: Only 1(2%) out of 48 patients with acute myelogenous leukemia showed abnormal band shift in exon 5 with PCR-SSCP. Base sequence of exon 5 of this patient with normal karyotype was found to have silent mutation at codon 143 from GTG(valine) to GTA(valine). He had acute myelogenous leukemia of M6 subtype and the leukemia was refractory to two cycles of standard induction chemotherapy, succumbed to death at last. CONCLUSION: Mutation of the p53 gene was found to be very rare in acute myelogenous leukemia in Korea and it was thought to be involved in leukemogensis only in some patients.

A case of malignant lymphoma with CNS involvement / 대한혈액학회지

No abstract available.

Acute myeloid leukemia following five years of aplastic anemia / 대한임상병리학회지

No abstract available.

Procoagulant activity and thrombelastography in korean hemorrhagic fever

Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease.