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2.  What do patients want from the National Health Insurance? 
The Korean Journal of Hematology  2010;45(4):217-218.
doi:10.5045/kjh.2010.45.4.217
PMCID: PMC3023043  PMID: 21253419
4.  Auer rod-like crystal inclusions in plasma cells of multiple myeloma 
doi:10.5045/kjh.2010.45.4.222
PMCID: PMC3023045  PMID: 21253421
5.  Plasmablastic plasma cell myeloma mimicking plasmablastic lymphoma 
doi:10.5045/kjh.2010.45.4.223
PMCID: PMC3023046  PMID: 21253422
6.  The immunobiology of cord blood transplantation 
The Korean Journal of Hematology  2010;45(4):224-235.
Despite significant recent advances in the applicability and outcome following unrelated cord blood transplantation (UCBT), infections remain a major cause of mortality associated with poor immune recovery in the first 6 months after UCBT. Enhanced immune reconstitution not only could improve survival by reduced transplant related mortality, but may also favorably impact on relapse incidence by improved graft-versus-leukemia effects. This review will summarize our current understanding of the biology of immune recovery post-UCBT with an emphasis on adaptive T cell dependent immunity. New efforts to boost immunity will be also highlighted including our own laboratory, where ex vivo T cell expansion is pursued towards adoptive immunotherapy.
doi:10.5045/kjh.2010.45.4.224
PMCID: PMC3023047  PMID: 21253423
Cord blood stem cell transplantation; Opportunistic infection; Immune reconstitution; Adoptive immunotherapy; Graft vs leukemia effect
7.  Outcome of childhood acute promyelocytic leukemia treated using a modified AIDA protocol 
The Korean Journal of Hematology  2010;45(4):236-241.
Background
Combination treatment with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy has led to major advances in the treatment of acute promyelocytic leukemia (APL).
Methods
In this study, we reviewed the outcome of pediatric APL patients treated using a modified AIDA protocol at our institution.
Results
Between May 1999 and December 2007, 23 patients were diagnosed with APL at the Department of Pediatrics, Saint Mary's Hospital, The Catholic University of Korea. Eleven patients were male (48%) (median age at diagnosis, 11 (range, 2-14) years). The treatment protocol consisted of remission induction (achieved by coadministration of ATRA and idarubicin), 3 courses of consolidation treatment, and 2 years of maintenance treatment during which ATRA was also administered. Three patients died early during remission induction due to CNS hemorrhage. The remaining 20 patients achieved complete remission (CR), with an overall CR rate of 87%. Two patients relapsed and died, and another patient died of pneumonia unrelated to APL. Four patients (17%) were diagnosed with ATRA syndrome, and all patients showed resolution of symptoms. The event-free survival (EFS) and overall survival (OS) of the cohort were 78.3±8.6% and 76.3±9.5%, respectively. Initial WBC count at diagnosis was the only significant prognostic factor for the rate of CR (P=0.039) and OS (P=0.039).
Conclusion
A modified AIDA protocol for the treatment of childhood APL leads to improved EFS and OS, with limited ATRA syndrome-associated toxicity. Active monitoring and treatment of patients with high initial WBC counts may help in reducing mortality.
doi:10.5045/kjh.2010.45.4.236
PMCID: PMC3023048  PMID: 21253424
Acute promyelocytic leukemia; Children; All-trans-retinoic acid; Anthracycline
8.  Incidence and clinical characteristics of clonal cytogenetic abnormalities of acquired aplastic anemia in adults 
The Korean Journal of Hematology  2010;45(4):242-246.
Background
Cytogenetic abnormalities (CAs) have been reported frequently in patients with otherwise typical aplastic anemia (AA), but their implications in the prognosis and in the evolution to hematologic malignancies are controversial.
Methods
We retrospectively analyzed 127 adult AA patients who had successful cytogenetic analysis at initial diagnosis.
Results
The patients were classified into 3 groups according to the initial and follow-up results of cytogenetic profiles. Group 1 included patients who had persistent AA with normal cytogenetic profiles (N=117); Group 2, those who had a normal cytogenetic profile at initial diagnosis but later acquired CA (N=4, 3.1%); and Group 3, those who had CA at the initial diagnosis, regardless of follow-up cytogenetic status (N=6,4.7%). In Group 2, 2 patients later developed CA without progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); the other 2 patients later progressed to AML. None of the patients in Group 3 progressed to AML or MDS. There was no significant difference in overall survival between Groups 1 and 3.
Conclusion
AA patients with CA at initial diagnosis or follow-up may not be at greater risk for evolution to AML or MDS, or show shorter survival periods. Prospective studies and a larger patient samples are needed to establish the clinical relevance of CA.
doi:10.5045/kjh.2010.45.4.242
PMCID: PMC3023049  PMID: 21253425
Aplastic anemia; Cytogenetic abnormality
9.  Role of p16 in the pathogenesis of Langerhans cell histiocytosis 
The Korean Journal of Hematology  2010;45(4):247-252.
Background
It has been hypothesized that genetic alteration at the cellular level may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of Langerhans cells (LCs).
Methods
We examined whether p16 protein expression can be used to predict the outcome of Langerhans cell histiocytosis (LCH). Archival paraffin blocks from children diagnosed with LCH and followed at the Asan Medical Center and Chungnam National University Hospital between March 1998 and February 2008 were studied.
Results
Slides were stained with p16 antibody and evaluated semi-quantitatively using the following scale: negative, no staining; ±, weakly positive; 1+, staining similar to lymphocytes surrounding the LCs; 2+, stronger staining than lymphocytes; 3+, much stronger staining than lymphocytes. Negative and ± groups were assigned to a lower expression group (LEG) and the 1+, 2+, and 3+ groups were assigned to a higher expression group (HEG). The median age of the 51 patients (24 girls, 27 boys) was 49 (range, 0.6-178) months, and LCH was diagnosed based on CD1a positivity. p16 protein was expressed to varying degrees in all but one specimen. There was a greater tendency toward multisystem disease, risk organ involvement, and relapse in the HEG than in the LEG.
Conclusion
The p16 protein may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of LCs, and thus may influence the clinical outcome and prognosis of LCH.
doi:10.5045/kjh.2010.45.4.247
PMCID: PMC3023050  PMID: 21253426
Genes; p16; Histiocytosis; Langerhans cells; Immunohistochemistry
10.  Additional rituximab-CHOP (R-CHOP) versus involved-field radiotherapy after a brief course of R-CHOP in limited, non-bulky diffuse large B-cell lymphoma: a retrospective analysis 
The Korean Journal of Hematology  2010;45(4):253-259.
Background
Standard treatment for stage I or non-bulky stage II diffuse large B-cell lymphoma (DLBCL) has been either a brief course of chemotherapy plus involved-field radiotherapy (IFRT) or prolonged cycles of chemotherapy. The introduction of rituximab has necessitated re-evaluation of the treatment for limited disease (LD) DLBCL.
Methods
Thirty-nine LD DLBCL patients (median age, 52 years; range, 24-85) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were retrospectively analyzed. Treatment outcomes were evaluated, and toxicity, event-free survival (EFS), and overall survival (OS) were compared according to the treatment and risk factors.
Results
The median follow-up duration was 34.6 months (range, 9.1-65.4). The 3-year EFS and OS were 76.0% and 86.0%, respectively. Among the 36 patients who underwent either 3-4 cycles of R-CHOP followed by IFRT (N=22) or 6-8 cycles of R-CHOP (N=14), there was no difference in the 3-year EFS (79.4% vs. 71.6%, P=0.638) and 3-year OS (85.7% vs. 92.9%, P=0.732). Severe neutropenia and neutropenic fever were more frequent in patients treated with R-CHOP alone, with 1 treatment-related mortality. Among the IFRT patients, 1 required hospital admission for IFRT-related complications. No events or deaths were reported among patients without adverse risk factors.
Conclusion
The difference in outcomes between the 2 treatment options was not significant. Analysis of treatment outcomes suggested that baseline characteristics and expected toxicities should be considered in LD DLBCL treatment. Further studies are needed to define the optimal treatment in the rituximab era.
doi:10.5045/kjh.2010.45.4.253
PMCID: PMC3023051  PMID: 21253427
Diffuse large B-cell lymphoma; Radiotherapy; Rituximab
11.  Diagnosis of non-overt disseminated intravascular coagulation made according to the International Society on Thrombosis and Hemostasis criteria with some modifications 
The Korean Journal of Hematology  2010;45(4):260-263.
Background
An early diagnosis of disseminated intravascular coagulation (DIC) before its progression to an overt stage is necessary for early treatment and positive outcomes. In 2001, the Scientific and Standardization Committee (SCC) of the International Society on Thrombosis and Hemostasis (ISTH) proposed new criteria for the preclinical diagnosis of overt and non-overt DICs. We investigated the clinical usefulness of the modified ISTH criteria for non-overt DIC diagnosis.
Methods
We enrolled 296 DIC patients (170 males and 126 females) admitted and evaluated at the Gangnam Severance Hospital, Seoul, Korea, between March 2006 and April 2007. Hemostatic tests, including platelet counts, prothrombin time (PT), D-dimer levels with antithrombin, and protein-C levels, were evaluated by excluding negative scores with clinical signs, in which more than 5 points of interest denoted non-overt DIC. Mortality rates were also evaluated.
Results
There were 289 patients with increased D-dimer levels and significant parametric changes suggesting DIC progression. Protein C and antithrombin levels were lower (99.2% each) and appeared earlier in patients with non-overt DIC than in patients with overt DIC. In all, 125 (43.3%) patients had non-overt DIC and, of which 27 died (mortality rate, 21.6%). The sensitivity and specificity for mortality were 73.0% and 55.9%, respectively, which were same as those for the original ISTH criteria.
Conclusion
The modified ISTH criteria can be used for the early detection of non-overt DIC, and may be useful for the improvement of outcomes of non-overt DIC patients.
doi:10.5045/kjh.2010.45.4.260
PMCID: PMC3023052  PMID: 21253428
Diagnosis; Non-overt disseminated intravascular coagulation; International Society on Thrombosis and Hemostasis (ISTH)
12.  Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis 
The Korean Journal of Hematology  2010;45(4):264-268.
Background
In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis.
Methods
TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA.
Results
We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7±9.3 ng/mL) than in samples from healthy individuals (10.5±5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis.
Conclusion
The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.
doi:10.5045/kjh.2010.45.4.264
PMCID: PMC3023053  PMID: 21253429
Sepsis; TAFI isoforms; TAFIa; TAFIai; Diagnosis
13.  The use of the complement inhibitor eculizumab (Soliris®) for treating Korean patients with paroxysmal nocturnal hemoglobinuria 
The Korean Journal of Hematology  2010;45(4):269-274.
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by chronic complement-mediated hemolysis. Eculizumab, a humanized monoclonal antibody against the terminal complement protein C5, potently reduces chronic intravascular hemolysis. We tested the clinical efficacy and safety of a 24-week treatment with eculizumab in 6 Korean patients with PNH.
Methods
We enrolled 6 patients with PNH who had clinically significant hemolysis. Eculizumab was administered intravenously at 600 mg/week for the first 4 weeks followed by 900 mg at week 5 and 2nd weekly thereafter.
Results
Three men and 3 women with a median age of 39.5 years (24-61 years) were enrolled. The median duration of PNH was 11 years (6-25 years). Hemolysis occurred in all patients [median lactate dehydrogenase (LDH) level, 7.95 times the upper limit of the reference range of LDH]. All patients treated with eculizumab had a rapid and sustained reduction in the degree of hemolysis. RBC transfusion requirements for 3 months were decreased from 0-12 units (median requirement, 1.5 units) to 0-6 units (median requirement, 0 units). Improvement in fatigue was noted in 4 patients. Further, 5 patients who had been receiving corticosteroids either reduced the dose or discontinued therapy. No significant adverse events related to eculizumab therapy were observed.
Conclusion
These results show that eculizumab reduces the degree of intravascular hemolysis, reduces or eliminates the requirement of RBC transfusion, and improves anemia and fatigue in patients with PNH. Eculizumab is an effective and safe option for treating Korean patients with PNH.
doi:10.5045/kjh.2010.45.4.269
PMCID: PMC3023054  PMID: 21253430
Paroxysmal nocturnal hemoglobinuria; Eculizumab; Efficacy; Safety
14.  Primary renal aspergillosis and renal stones in both kidneys associated with hematopoietic stem cell transplant 
The Korean Journal of Hematology  2010;45(4):275-278.
Invasive aspergillosis (IA) is a leading cause of infectious mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT); the mortality due to IA ranges from 70% to 93% in HSCT patients. Early diagnosis and treatment are the cornerstones for the good prognosis of IA. Primary renal aspergillosis is an extremely rare presentation in patients who have undergone HSCT, and the risk factor for this uncommon presentation is not well known. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after a nephrectomy, which was performed to treat massive renal hematoma.
doi:10.5045/kjh.2010.45.4.275
PMCID: PMC3023055  PMID: 21253431
Primary renal aspergillosis; Hematopoietic stem cell transplant; Renal stones
15.  Wernicke's encephalopathy following allogeneic hematopoietic stem cell transplantation 
The Korean Journal of Hematology  2010;45(4):279-281.
Wernicke's encephalopathy is caused by thiamine deficiency, and is characterized by acute mental confusion, ataxia, and ophthalmoplegia. It is also a rare neurologic complication of hematopoietic stem cell transplantation (HSCT). However, because of its rare incidence, Wernicke's encephalopathy can easily be overlooked in HSCT patients, and a few misleading steps in the early stage of the disease may result in permanent neurologic disability or even mortality. We recently encountered a case of Wernicke's encephalopathy in a patient who underwent allogeneic HSCT. Based on our own experience and previously published documents, we suggest early radiologic surveillance and treatment for patients with findings compatible with Wernicke's encephalopathy following HSCT.
doi:10.5045/kjh.2010.45.4.279
PMCID: PMC3023056  PMID: 21253432
Wernicke's encephalopathy; Hematopoietic stem cell transplantation; Thiamine
16.  Long-term disease-free survival of patients with primary cardiac lymphoma treated with systemic chemotherapy and radiotherapy 
The Korean Journal of Hematology  2010;45(4):282-285.
Primary cardiac lymphoma (PCL) is a rare disease entity with only a few reported cases in Korea. In this paper, we report a case of PCL in a 59-year-old man presenting with chest pain. Diffuse large B-cell lymphoma was diagnosed through a cardiac catheterization-assisted percutaneous endomyocardial biopsy, and there was no evidence of extracardiac involvement of the lymphoma.The patient had a complete clinical response after systemic chemotherapy with a rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen and additional post-chemotherapeutic radiation therapy. The patient experienced a long-term disease-free survival of over 4 years. However, he received coronary artery bypass graft surgery due to an acute myocardial infarction that occurred 3 years after the completion of the radiation therapy. Although the addition of radiation therapy to the treatment is thought to decrease the risk of relapse in patients with PCL, a careful and thorough consideration of the potential complications of radiation therapy, particularly with respect to cardiac complications, should be considered.
doi:10.5045/kjh.2010.45.4.282
PMCID: PMC3023057  PMID: 21253433
Lymphoma; Myocardial infarction; Drug therapy; Radiotherapy
18.  Clinical utility of FISH analysis in addition to G-banded karyotype in hematologic malignancies and proposal of a practical approach 
The Korean Journal of Hematology  2010;45(3):171-176.
Background
Fluorescence in situ hybridization (FISH) analysis can provide important information in the management of patients with hematologic malignancies. However, FISH performed in addition to G-banded karyotype can be labor-intensive and expensive. The aim of this study was to evaluate whether FISH gives additional information in the setting of adequate conventional cytogenetics in cases of hematologic malignancies.
Methods
Bone marrow aspirates were obtained from 135 patients at diagnosis (56 AML, 32 MDS, 20 ALL, and 27 MM) between 2005 and 2010. Interphase FISH was performed using the following probes: BCR/ABL1, AML1/ETO, PML/RARA, CBFB, MLL, EGR1, CEP8, and D7S486 for AML; CEP8, D20S108, EGR1, and D7S486 for MDS; BCR/ABL1, MLL, CDKN2A (p16), ETV6, and 6q21/c-myc for ALL; IgH, TP53, D13S25, IgH/CCND1, IgH/MAF, IgH/FGFR3, and 1q21/8p21 for MM. We compared the results of FISH with the corresponding aberrations identified by G-banded karyotype.
Results
Additional genetic aberrations detected by FISH (which were not identified by G-banded karyotype) were 4%, 9%, 50%, and 67% in AML, MDS, ALL, and MM, respectively. In ALL, CDKN2A and ETV6 FISH revealed additional genetic aberrations in 33% and 28% of cases, respectively. In MM, FISH was of benefit in detecting IgH, D13S25, TP53, and 1q21 rearrangements, not detected by G-banded karyotype (31%, 36%, 20%, and 40%, respectively).
Conclusion
These results suggest that performing FISH in addition to G-banded karyotype may contribute little additional genetic information in AML and MDS, whereas routine FISH analysis appears to be an efficient screening method in ALL and MM.
doi:10.5045/kjh.2010.45.3.171
PMCID: PMC2983032  PMID: 21120205
FISH; Karyotype; Acute myeloid leukemia; Myelodysplastic syndrome; Acute lymphoblastic leukemia; Multiple myeloma
19.  Erratum 
doi:10.5045/kjh.2010.45.3.213
PMCID: PMC2983033  PMID: 21120214
21.  Bortezomib and melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma 
The Korean Journal of Hematology  2010;45(3):183-187.
Background
High-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT) is the standard treatment for young patients with multiple myeloma (MM). However, the response rates after ASCT are often unsatisfactory. We performed a pilot study by using bortezomib-melphalan as conditioning regimen for ASCT in Korean patients with MM.
Methods
The conditioning regimen consisted of administration of intravenous infusion of bortezomib 1.0 mg/m2 on days -4 and -1 and melphalan 50 mg/m2 (day -4) and 150 mg/m2 (day -1). In this study, we enrolled 6 newly diagnosed patients and 2 patients with relapse.
Results
The disease status of the 6 newly diagnosed patients at ASCT was as follows: 1 complete remission (CR), 1 very good partial remission (VGPR), and 4 partial remissions (PRs). The disease status of the 2 relapsed patients at ASCT was PR. All patients except 1 showed adequate hematologic recovery after ASCT. The median time for the absolute neutrophil counts to increase over 500/mm3 was 13 days (range, 10-19 days). Six patients with VGPR or PR at the time of transplantation showed an improvement in response to CR after ASCT. The patients were followed up without any maintenance treatment after ASCT except 1 patient who died during ASCT. During the follow-up period, CR was maintained in 3 newly diagnosed patients, but the other 4 patients, including 2 newly diagnosed patients, relapsed.
Conclusion
Conditioning regimen consisting of bortezomib and melphalan may be effective for ASCT in MM; however, the feasibility of this regimen should be further evaluated in large study populations.
doi:10.5045/kjh.2010.45.3.183
PMCID: PMC2983035  PMID: 21120207
Multiple myeloma; Bortezomib; Melphalan
22.  Image analytic study of nuclear area in mantle cell lymphoma 
The Korean Journal of Hematology  2010;45(3):193-196.
Background
Malignant lymphomas are classified on the basis of morphology, immunohistochemistry, and genetic and molecular biological features. Morphology is considered the most important and basic feature. Lymphomas can be classified as small, medium, or large depending on the cell size, but this criterion tends to be rather subjective. The aim of this study was to investigate the usefulness of an objective approach based on quantitative measurements.
Methods
Twenty specimens of mantle cell lymphoma and 2 specimens of the tonsil were examined. The nuclear area of 6,401 tumor cells of mantle cell lymphoma and 743 normal mantle cells of reactive tonsils were measured by 3 authors by using a user-controlled image-analyzer. The images of the nuclei were outlined using the spline method and the i-solution software, and the data were assessed using ANOVA and Student's t-test.
Results
The mean nuclear areas of mantle cell lymphoma cells measured by the 3 authors were 37.9 [7.9] µm2, 37.9 [7.2] µm2, and 38.2 [7.7] µm2 and those of normal mantle cells in reactive tonsil were 28.6 [2.3] µm2, 28.8 [2.0] µm2, and 27.0 [3.0] µm2. There was no statistical difference between the 3 observations of mantle cell lymphoma (P=0.580) and normal tonsils.
Conclusion
For morphology, nuclear area is considered an important feature in the classification schemes of lymphoma. We showed that nuclear area measurement by using image analyzer can be used as an objective quantitative method. We think that nuclear morphometry may play a significant role in the diagnosis of lymphoma.
doi:10.5045/kjh.2010.45.3.193
PMCID: PMC2983036  PMID: 21120209
Image analysis; Morphometry; Nuclear area; Mantle cell lymphoma
23.  Long-term outcomes of a 5-year follow up of patients with immune thrombocytopenic purpura after splenectomy 
The Korean Journal of Hematology  2010;45(3):197-204.
Background
The long-term outcomes of adult patients with immune thrombocytopenic purpura (ITP) after splenectomy are not clear.
Methods
We retrospectively analyzed 31 patients who underwent splenectomy after diagnosis of ITP at our institution between 1990 and 2009. Long-term follow-up was defined as a follow-up that lasted 1 year or more from splenectomy to the last follow-up.
Results
The overall response rate to splenectomy was 84%. However, the response rate at 6 and 12 months decreased to 77% and 68%, respectively. During the 6 years of median follow-up after splenectomy, 11 patients (35%) relapsed. The long-term response rate was 55%. The long-term follow-up of 26 patients after responding to splenectomy showed that the median time from splenectomy to relapse was 19 months in the partial response (PR) group; however, there was no relapse after 9 months in the complete response (CR) group. Variables, including age, were not predictive of the long-term response after splenectomy. Additional treatment in patients who did not respond or relapsed after splenectomy was mostly effective. After a median follow-up of 7 years (range: 1-25 years) from the diagnosis, there were 2 deaths, including one due to spontaneous bleeding after repair of duodenal ulcer perforation.
Conclusion
Although splenectomy is safe and effective, the response rate after splenectomy continuously decreases over time. The duration of response is different between the patients that achieved CR and those that achieved PR. Factors, including age, were not predictors of a response to splenectomy.
doi:10.5045/kjh.2010.45.3.197
PMCID: PMC2983037  PMID: 21120210
Adult; Immune thrombocytopenic purpura; Long term; Splenectomy; Thrombocytopenia
24.  Current trends in domestic status and insurance policy for use of plasma 
The Korean Journal of Hematology  2010;45(3):147-149.
doi:10.5045/kjh.2010.45.3.147
PMCID: PMC2983038  PMID: 21120199
25.  Induction of hypoxia-inducible factor-1α inhibits drug-induced apoptosis in the human leukemic cell line HL-60 
The Korean Journal of Hematology  2010;45(3):158-163.
Background
Leukemic cells originate from hypoxic bone marrow, which protects them from anti-cancer drugs. Although many factors that cause drug resistance in leukemic cells have been studied, the effect of hypoxia on drug-induced apoptosis is still poorly understood.
Methods
In this study, we examined the effect of hypoxia on anti-leukemic drug resistance in leukemic cell lines treated with cobalt chloride (CoCl2), a hypoxia-mimetic agent. Cellular proliferation was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and western blots were performed to investigate apoptosis-related proteins.
Results
Unlike its previously known apoptotic effect, the expression of HIF-1α increased the survival rate of human promyelocytic leukemia HL-60 cells when these cells were exposed to anti-leukemic drugs; these effects were mediated by heat-shock protein HSP70 and the pro-apoptotic protein Bax.
Conclusion
These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.
doi:10.5045/kjh.2010.45.3.158
PMCID: PMC2983039  PMID: 21120203
Hypoxia; Arsenic trioxide; HIF-1α; Cobalt chloride; Bax; HSP70

Results 1-25 (68)