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1.
Article in English | WPRIM | ID: wpr-915802

ABSTRACT

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

2.
Article in English | WPRIM | ID: wpr-919169

ABSTRACT

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare but severe complication of hematopoietic cell transplantation (HCT) showing high mortality. Multiple risk factors for SOS/VOD were identified, but it is often confused with other hepatic complications due to nonspecific clinical features. Therefore, diagnostic and severity criteria have been revised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of development within 21 days, emphasizes late-onset SOS/VOD, and suggests the importance of Doppler ultrasonography. The severity criteria were further subdivided for guidance to begin active treatment using defibrotide which was approved in Korea since 2016. In a phase 3 trial, defibrotide had superior 100-day survival, compared to best available treatments (38.2% vs. 25.0%). Although several studies of SOS/VOD in Korean patients have been performed after the implementation of HCT, most involved small number of pediatric patients. Recently, the Korean Society of Blood and Marrow Transplantation investigated the incidence of SOS/VOD in the Korean population, and several influential studies of adult patients were published. Here, we summarize recent issues regarding the mechanism, diagnosis, severity criteria, prevention, and treatments of SOS/VOD in Korean patients, as well as recent analyses of nationwide incidence.

3.
Article in English | WPRIM | ID: wpr-919162

ABSTRACT

Background/Aims@#Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population. @*Methods@#We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians. @*Results@#No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period. @*Conclusions@#Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.

4.
Article in English | WPRIM | ID: wpr-875517

ABSTRACT

Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods: We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusions: This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

5.
Article in English | WPRIM | ID: wpr-875436

ABSTRACT

In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.

6.
Article | WPRIM | ID: wpr-831913

ABSTRACT

Background/Aims@#Various preoperative screening tests, such as platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time, have been widely used to evaluate the risk of bleeding during surgery. Use of platelet function analyzer (PFA)-100/200 for assessing platelet function instead of bleeding time is increasing. However, its role in predicting the perioperative risk of bleeding remains controversial. @*Methods@#Data of 703 patients who underwent surgery under general anesthesia were retrospectively analyzed. Preoperative platelet function was measured using PFA-200 system and the association with intraoperative bleeding was assessed. Additionally, other variables that could affect PFA-200 results were assessed by logistic regression analysis. @*Results@#Collagen/epinephrine (COL/EPI) test was prolonged in 199/703 (28.3%) patients (EPI group), while 99/212 (46.7%) patients showed COL/adenosine diphosphate test abnormalities. Bleeding over 300 mL during surgery occurred in 14.3% and 20.1% of patients in the normal and EPI groups, respectively (p = 0.058). In addition, red blood cell transfusion within 72 hours after surgery rate was significantly higher in the EPI group than in the normal group (31.7% vs. 23.4%,p= 0.024). In multivariate logistic analysis, prolongation closure time with COL/EPI (p = 0.068) was marginally associated with risk of bleeding during surgery. Furthermore, PFA-200 results were influenced by various factors, such as nonsteroidalanti-inflammatory drug use, blood group, hematocrit, and time of blood collection. @*Conclusions@#Preoperative PFA-200 test may be helpful in predicting the risk of perioperative bleeding. However, its results should be carefully interpreted becausethey are affected by several factors.

7.
Article | WPRIM | ID: wpr-831794

ABSTRACT

Background/Aims@#The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP. @*Methods@#We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis. @*Results@#The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points. @*Conclusions@#IPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

8.
Article | WPRIM | ID: wpr-831757

ABSTRACT

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders characterized by the overproduction of mature blood cells that have an increased risk of thrombosis and progression to acute myeloid leukemia. Next-generation sequencing studies have provided key insights regarding the molecular mechanisms of MPNs. MPN driver mutations in genes associated with the JAK-STAT pathway include JAK2 V617F, JAK2 exon 12 mutations and mutations in MPL, CALR, and CSF3R. Cooperating driver genes are also frequently detected and also mutated in other myeloid neoplasms; these driver genes are involved in epigenetic methylation, messenger RNA splicing, transcription regulation, and signal transduction. In addition, other genetic factors such as germline predisposition, order of mutation acquisition, and variant allele frequency also influence disease initiation and progression. This review summarizes the current understanding of the genetic basis of MPN, and demonstrates how molecular pathophysiology can improve both our understanding of MPN heterogeneity and clinical practice.

9.
Article in English | WPRIM | ID: wpr-763148

ABSTRACT

PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). MATERIALS AND METHODS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system. RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group. CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.


Subject(s)
Animals , Annexin A5 , Cell Line , Colon , Dendritic Cells , Immune System , Immunotherapy , Injections, Intradermal , Leg , Methods , Mice , Phagocytosis , Radiation Dosage , Radiosurgery , Survival Rate , T-Lymphocytes , Vaccination
10.
Article in English | WPRIM | ID: wpr-919111

ABSTRACT

BACKGROUND/AIMS@#Bortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment modification is often needed owing to adverse events. The aim of this study was to investigate the clinical outcomes of modifying the dose of melphalan-prednisone (MP) in patients receiving VMP.@*METHODS@#We examined 67 patients who received a modified dose of MP, and 38 patients who received the regularly planned dose of MP. We then analyzed clinical differences between the groups.@*RESULTS@#Although there was no difference in the proportion of discontinuation due to adverse events between dose groups, more patients in the planned-dose group experienced earlier discontinuation in general. The overall response rate (ORR) was 81.0% and complete response (CR) rate was 30.5%. After a median 15.7 months of follow-up, the median progression-free survival (PFS) and overall survival (OS) were 25.0 and 47.8 months, respectively. There was no significant difference in the ORR, CR, PFS, and OS of the two dose groups. A median of four cycles were delivered, and the median cumulative bortezomib dose was 41.6 mg/m². The median PFS in patients with doses ≥ 41.6 mg/m² was longer than that in patients with doses < 41.6 mg/m² (35.1 months vs. 9.6 months). However, when MP was < 50% of the planned dose, PFS and OS were poor.@*CONCLUSIONS@#Modifying the dose of MP might be a feasible and effective therapeutic approach for multiple myeloma patients receiving VMP treatment.

11.
Korean Journal of Medicine ; : 182-190, 2019.
Article in Korean | WPRIM | ID: wpr-741135

ABSTRACT

BACKGROUND/AIMS: The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods. METHODS: We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis. RESULTS: Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003). CONCLUSIONS: This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.


Subject(s)
Biopsy , Bone Marrow , Diagnosis , Humans , Korea , Lymphoma , Lymphoma, Non-Hodgkin , Methods , Multivariate Analysis , Prognosis , Retrospective Studies
13.
Journal of Liver Cancer ; : 130-141, 2018.
Article in English | WPRIM | ID: wpr-765693

ABSTRACT

BACKGROUND/AIMS: To evaluate the technical feasibility of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) with the major portal vein tumor thrombosis (PVTT). METHODS: Ten institutions affiliated with the Korean Stereotactic Radiosurgery Group were provided the contours of four cases: the first case was the first branch PVTT with sufficient normal liver volume (NLV), the second was the first branch PVTT with insufficient NLV, the third was the main trunk PVTT at confluence level, and the fourth was the main trunk PVTT with entire length. The institutions were asked to make SBRT plans according to their current treatment protocols and to complete facility questionnaires. RESULTS: Based on institutional protocols, SBRT was feasible in nine institutions for the first case (32–60 Gy in 3–5 fractions), in eight institutions for the second case (32–50 Gy in 3–5 fractions), in seven institutions for the third case (35–60 Gy in 3–5 fractions), and in four institutions for the fourth case (35–42 Gy in 4–5 fractions). The other institutions recommended hypo- or conventional fractionation due to insufficient NLV or gastrointestinal organ proximity. With analysis of the SBRT dose to the central hepatobiliary tract, the major PVTT could theoretically be associated with a high risk of hepatobiliary toxicity. CONCLUSIONS: Although SBRT is a technically feasible option for HCC with the major PVTT, there was a variability among the participating institutions. Therefore, further studies will be necessary to standardize the practice of SBRT for the major PVTT.


Subject(s)
Carcinoma, Hepatocellular , Clinical Protocols , Liver , Portal Vein , Radiosurgery , Thrombosis
14.
Blood Research ; : 207-211, 2017.
Article in English | WPRIM | ID: wpr-38721

ABSTRACT

BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.


Subject(s)
Anemia, Aplastic , Cohort Studies , Flow Cytometry , Follow-Up Studies , Hemoglobinuria, Paroxysmal , Hemolysis , Humans , Prospective Studies
15.
Article in English | WPRIM | ID: wpr-67785

ABSTRACT

BACKGROUND/AIMS: The aims of this study were to identify the value of inflammatory markers as pretreatment prognostic factors for patients with multiple myeloma (MM) and to estimate the value of a prognostic index including these markers at diagnosis. METHODS: A total of 273 newly diagnosed MM patients undergoing active treatment were analyzed in this study. The prognostic values for survival of the pretreatment inflammatory markers were investigated. A myeloma prognostic index (MPI) was derived using prognostic factors determined to be independently significant on multivariate analysis. RESULTS: A high pretreatment neutrophil-lymphocyte ratio (NLR), low platelet count, and high C-reactive protein (CRP) level had independently unfavorable significance for overall survival (OS). The MPI was derived based on these factors. Per the MPI, 1 point each was assigned to high NLR, low platelet count, and high CRP. Risk categories were stratified into low- (score 0), intermediate- (score 1), and high-risk (score 2 or 3) groups. The MPI demonstrated independent statistical significance for OS on multivariate analysis ([intermediate: hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.12 to 3.24] and [high: HR, 3.37; 95% CI, 2.00 to 5.69]; p < 0.001). Moreover, this significance could be observed regardless of age, renal function, and exposure to novel agents. In addition, the International Staging System risk group could be further significantly stratified using the MPI. CONCLUSIONS: The MPI, consisting of pretreatment inflammatory markers, NLR, platelet count, and CRP, might be effective in predicting the survival of newly diagnosed MM patients undergoing active treatment.


Subject(s)
C-Reactive Protein , Diagnosis , Humans , Multiple Myeloma , Multivariate Analysis , Platelet Count , Prognosis
16.
Article in English | WPRIM | ID: wpr-67784

ABSTRACT

BACKGROUND/AIMS: Although multiple myeloma (MM) is typically a disease of the elderly, a certain subset of extremely young patients exists. It is necessary to establish clinicopathological characteristics for this population. METHODS: We reviewed the medical records of MM patients whose age was 40 years or younger at diagnosis. RESULTS: A total of 32 patients were analyzed (male to female ratio 19:13, median age 37 years). According to International Staging System, 29%, 48%, and 16% were in stage I, II, and III, respectively. Light chain myeloma accounted for 30%. Clinically significant anemia, hypercalcemia, azotemia, and hypoalbuminemia were present in 29%, 28%, 13%, and 28%, respectively. Three or more lytic bone lesions were detected in 45% of the patients, whereas 13% had no lytic bone lesions. Regarding treatment, 79% of patients received autologous hematopoietic stem cell transplantation. After a median follow-up duration of 64 months, the 1-, 3-, and 5-year overall survival (OS) rates were 84%, 62%, and 54%, respectively. The median OS was 61 months for the entire cohort. CONCLUSIONS: In our study, MM patients aged 40 years or younger at diagnosis showed no superior survival compared to those of the moderately elderly patients based on historical data.


Subject(s)
Aged , Anemia , Azotemia , Cohort Studies , Diagnosis , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Humans , Hypercalcemia , Hypoalbuminemia , Medical Records , Multiple Myeloma , Treatment Outcome , Young Adult
17.
Korean Journal of Medicine ; : 480-483, 2017.
Article in Korean | WPRIM | ID: wpr-119544

ABSTRACT

Acquired factor V deficiency is extremely rare. Here we report the case of an 88-year-old female patient who presented with hematochezia 1 month after undergoing percutaneous coronary intervention. Her laboratory results showed an extremely prolonged prothrombin time and an activated partial thromboplastin time, but neither improved after fresh frozen plasma transfusion. She was finally diagnosed with acquired factor V deficiency and successfully treated with an immunosuppressant.


Subject(s)
Aged, 80 and over , Blood Coagulation Factor Inhibitors , Factor V Deficiency , Factor V , Female , Gastrointestinal Hemorrhage , Humans , Partial Thromboplastin Time , Percutaneous Coronary Intervention , Plasma , Prothrombin Time
18.
Article in Korean | WPRIM | ID: wpr-123562

ABSTRACT

Influenza infection may be complicated by various infectious or non-infectious diseases. Among them, hemophagocytic lympho-histiocytosis (HLH) is an uncommon hyperinflammatory syndrome caused by uncontrolled proliferation and activation of macrophages and lymphocytes, and it is often life threatening. A previously healthy male patient was suspected to have HLH after influenza B infection. The diagnosis was established based on clinical diagnostic criteria suggested in the HLH-2004 trial. Despite prompt antiviral therapy, the patient expired on day 19 of hospitalization. Influenza can thus be complicated by HLH. Due to the non-specific manifestations of HLH, clinical suspicion and early diagnosis are important.


Subject(s)
Diagnosis , Early Diagnosis , Hospitalization , Humans , Influenza, Human , Lymphocytes , Lymphohistiocytosis, Hemophagocytic , Macrophages , Male
19.
Article in English | WPRIM | ID: wpr-109562

ABSTRACT

BACKGROUND/AIMS: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. METHODS: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. RESULTS: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-kappaB (NF-kappaB) and beta-catenin. CONCLUSIONS: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappaB and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Benzoates/pharmacology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Imatinib Mesylate/pharmacology , Iron Chelating Agents/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Triazoles/pharmacology
20.
Korean Journal of Medicine ; : 281-287, 2016.
Article in Korean | WPRIM | ID: wpr-167773

ABSTRACT

Philadelphia chromosome-negative classical myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In recent years, there have been major advances in our understanding of the molecular pathophysiology of these rare subgroups of myeloproliferative neoplasms. The World Health Organization diagnostic criteria were revised in 2008, and incorporated new somatic mutations of JAK2 V617F, found in most patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis. Subsequently, other mutations (MPL W515 and CALR) were discovered and this led to substantial changes in the diagnosis and treatment guidelines. This article reviews the diagnostic criteria for Philadelphia chromosome-negative classical myeloproliferative neoplasms, and changes in the diagnostic algorithm for clinical practice in Korea.


Subject(s)
Diagnosis , Humans , Korea , Polycythemia Vera , Primary Myelofibrosis , Thrombocythemia, Essential , World Health Organization
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