Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines

정낙균,Sol-Rim Jeon,이재욱,장필상,조빈,정대철 대한혈액학회 2015 Blood Research Vol.50 No.1

BackgroundAlthough deferasirox (DFX) is reported to have anti-tumor effects, its anti-leukemic activityremains unclear. We evaluated the effect of DFX treatment on two murine lymphoidleukemia cell lines, and clarified the mechanisms underlying its potential anti-leukemicactivity. MethodsL1210 and A20 murine lymphoid leukemia cell lines were treated with DFX. Cell viabilityand apoptosis were evaluated by the 3-(4,5-dimethylthaizol-2-yl)-5-(3-carboxymethylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and fluorescence-activated cellsorting (FACS) analysis, respectively. Immunoblotting was performed to detect the expressionof key apoptotic proteins. ResultsIn dose- and time-dependent manner, DFX decreased viability and increased apoptosisof murine leukemic cells. Fas expression was significantly higher in A20 cells than in L1210cells at all DFX concentrations tested. Although both cell lines exhibited high caspase 3and caspase 9 expression, a critical component of the intrinsic mitochondrial apoptoticpathway, expression was greater in L1210 cells. In contrast, caspase 8, a key factor in theextrinsic apoptotic pathway, showed greater expression in A20 cells. Cytochrome c expressionwas significantly higher in L1210 cells. In both cell lines, co-treatment with ferricchloride and DFX diminished the expression of these intracellular proteins, as comparedto DFX treatment alone. ConclusionTreatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemiacell lines, with differing apoptotic mechanisms in each cell line.

림프절 종대

정낙균 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.8

Lymphadenopathy is a common problem in children and adolescents. A wide variety of diseases and conditions may present as lymphadenopathy and an understanding of these conditions is essential to determine the most appropriate diagnostic work-up for each patient. A detailed history and physical examination with careful attention to the anatomical regions drained by the involved lymph node or mass often leads to the appropriate diagnosis. A majority of these children will prove to have a benign disorder; however, it is important for the pediatrician to have an appreciation for the malignant diseases or serious systemic illnesses that may initially present with lymphadenopathy, to ensure the timely diagnosis of a serious disease.

동종 골수이식 후 후기 거부반응을 보인 재생불량성 빈혈환아에서 동종 G-CSF 가동화 말초혈 조혈모세포이식 후 생착을 보인 1례

정낙균,조빈,정대철,김학기 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.1

중증 재생불량성 빈혈의 가장 효과적인 치료는 조직적합성 항원이 일치하는 형제자매의 골수이식이지만 골수이식 후에 거부반응으로 기대한 효과를 보지 못하는 경우 구제요법으로 수년 전까지만 해도 면역억제를 목적으로 방사선을 포함한 강력한 전처치 후에 동종 골수이식을 재시행 하였으나 성공률이 떨어지며 전처치로 인해 심각한 부작용을 초래하는 등 문제점이 있었다. 그러나 최근에는 가동화된 말초혈 조혈모세포이식이 보편화됨에 따라 동종 골수이식 후 생착부전이 있는 경우 강력한 전처치없이 재차 가동화된 말초혈 조혈모세포를 이식하는 방법으로 생착에 성공한 사례들이 국내외에서 보고되고 있으며, 특히 가동화된 말초혈 조혈모세포이식은 골수이식의 경우보다 조기 생착을 보이며 면역적인 면에서도 빠른 회복을 보이는 것으로 알려져 있다. 저자들은 동종 골수이식 후 후기 거부반응을 보인 중증 재생불량성 빈혈 환아에서 골수 공여자에게 G-CSF를 투여하여 가동화된 말초혈 조혈모세포를 이식하여 구제요번에 성공한 1례를 경험하여 보고하는바이다. 환아는 내원 4년7개월 전 중등도 재생불량성 빈혈로 진단되어 본원에서 항림프구 글로불린으로 치료 받았으며 치료 3개월 후 완전관해를 보였으나 18개월 이후 다시 악화되며 중증 재생불량성 빈혈의 소견을 보였다. 남동생과 조직적합성 항원이 일치하여 procarbazine, 항흉선세포 글로불린 및 cyclophosphamide 로 전처치 후 내원 17개월 전 동종 골수이식을 시행하였다. 환자에게 주입된 세포수로는 단핵구는 1.09×10^(8)/㎏, CD34+세포는 6.65×10^(6)/㎏이었으며 이식편대숙주반응을 예방하기 위하여 CSA와 methotrexate를 사용하였다. 이식 후 7개월까지는 급성 및 만성 이식편대숙주반응없이 성공적인 생착 소견을 보였으나 이후 혈소판의 수치가 감소하기 시작하면서 12개월 이후에는 다시 수혈이 필요한 정도로 전혈구의 수가 감소하였다. 입원직전 시행한 골수검사에서도 적혈구,백혈구, 혈소판들의 전구세포들이 모두 관찰되기는 하나 세포밀도가 20%이하로 감소되어있었으며 PCR-RFLP검사에서도 지속적으로 공여자와 환아의 혼합된 양상으로 나타나는 후기 거부반응의 소견을 보였다. 구제요법으로 골수이식과 동일한 공여자로부터 G-CSF가동화된 말초혈 조혈모세포이식을 시행하기위해 전처치로 750 cGy의 total nodal irradiation (TNI)를 시행하고 ATG를 4일간 투여하였다. 환아에게 ATG를 투여하기 시작한 다음날부터 공여자에게는 rhG-CSF(GrasynR)를 10㎍/㎏/day의 용량으로 6일간 투여하였으며 투여 5일째부터 말초혈에서 조혈모세포 및 단핵구를 3일에 걸쳐 채집하여 환자의 중심정맥을 통하여 투여하였다. G-CSF를 투여하고 조혈모 세포를 채집하는 기간중 공여자에게 특별한 이상 소견은 없었으며 환아에게 이식된 단핵구 및 CD34+ 조혈모세포수는 각각 환아의 몸무게 ㎏당 18.5×10^(8), 14.7×10^(6)이었다. 이식편대 숙주반응을 예방하기 위하여 CSA를 사용하였으며 이식 후 3일부터 말초혈액 백혈구수가 1,000/㎣으로 증가하였다. 이식 5일 후부터 GM-CSF 250㎍을 환아에게 피하 주사하였으며 이식 12일 이후 특별한 수혈 없이 혈소판수가 50,000/㎣이상으로 계속 유지되었고 이식편대 숙주반응은 나타나지 않았다. 이식 후 21일에 시행한 골수검사에서도 세포밀도 80%에 적혈구, 백혈구, 혈소판들의 전구세포들이 모두 관찰되는 생착 소견을 보였다. 환아는 이후 급성 이식편대 숙주반응 등의 특별한 이상소견 없이 이식 후 2개월이 지난 현재까지 건강하게 지내고 있다. 저자들은 동종 골수이식 후 후기 거부반응을 보인 재생불량성 빈혈 환아에서 TNI 및 ATG로 전처치 후 공여자에게 G-CSF를 투여하여 가동화된 말초혈 조혈모세포를 이식하여 생착을 보인 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is the treatment of choice in children with severs aplastic anemia(SAA). However, insufficient graft function owing to rejection remains an important and life-threatening complication following BMT for SAA. In that case, recent clinical studies have shown more rapid engraftment and faster recovery of the immune system after allogeneic transplantation of peripheral blood stem cells (PBSC) compared with BMT for the treatment of graft rejection. Here we report a case of successful transplatation of allogeneic granulocyte colony-stimulating factor (G-CSF) mobilized PBSC after engraftment failure of allogeneic BMT. A 7-year old male underwent allogeneic BMT for SAA from his HLA-and blood groupidentical brother. He was conditioned with cyclophosphamide, procarbazine and anti-thymocyte globulin (ATG, PAsteur). Post-transplant immunosuppression for graft versus host disease(GVHD) consisted of cyclosporine A (CSA) and a short course of methotrexate. Initially, the engraftment was sucessful until 7 months after BMT without any sign of acute and chronic GVHD. However, he failed to achieve durable trilineage hematopoietic engraftment. Evaluation of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) revealed mixed chimerism. 17 months after the first BMT, G-CSF primed PBSC from the same donor (cell dose 18.5×10^(8)/㎏ mononuclear, 14.7×10^(6)/㎏ CD34^(+) cells) was given after preparation with ATG and total nodal irradiation (TNI, 750 cGy). No side effects related to G-CSF administration or apheresis were observed in the donor. CSA was used for GVHD prophylaxis. To promote marrow recovery, granulocyte-macrophage CSF (GM-CSF, 250㎍/㎡) was administered from day +5 after the PBSC transfusion. The WBC count exceeded 1,000/㎣ on day +3 and the platelet count exceeded 50,000/㎣ on day +12 without transfusion. On day +21, BM histology showed a cellularity of 80% with trilineage engraftment. The patient is currently well with a stable engraftment 2 months following allogeneic PBSCT, without any sign of acute GVHD.

High-dose chemotherapy with reduced-dose craniospinal radiotherapy in children with newly diagnosed high-risk brain tumor

정낙균 대한혈액학회 2010 Blood Research Vol.45 No.3

Badminton 競技의 技術 內容에 關한 硏究 : 中學校, 國民學校 競技를 中心으로 In the game of primary and middle school

鄭洛均 圓光大學校 附設 體力科學硏究所 1983 體力科學硏究 Vol.6 No.-

This study is to analyse a single and double game which the player take part in the 12th national girls, and boys anathletic contest to search what to be important technique in the game. The conclusion is as the following. 1. In the case of a single game, the imporiant techniques in average 900 rounds show high clear 173.8 rounds(19.3%), Drop 147.5 rounds(16.4%), long service 144.5 rounds(16.1%), under clear 134.5 rounds(14.9%), in order. In the case of a double game, in average 1,427 rounds they show smash 286.8 rounds(20.1%), drive 262.5 rounds(18.4%), under clear 205.8 rounds(14.4%), high clear 180.8 rounds(12.7%), in order. 2. In the important techniques of each team, the primary girl students in a single game show high clear 25.4%, long service 16.8%, drop 14.4%, under clear 12.8%, in the rate. The middle girl students show smash 21.0%, drive 18.8%, under clear 13.4%,in the rate. 3. In the succes number and rate, the sungle game, show smash 23-29 rounds(18-31%), drop 15-34 rounds(14-33%), high clear 10-29 rounds (14-39%). The double game 47-73 rounds(19-30%), drive 24-49 rounds(18-37%), under clear 13-20 rounds(20-31%). 4. In the failure number and rate, the single game shows under clear 40-63 rounds(21-34%), under drive 15-31 rounds (17-34%), drop 15-18 rounds (19-23%). The double game shows under clear 39-85 rounds (16-33%), under drive 21-32 rounds (20-30%), drive 11-19 rounds (19-32%). 5. The average time required in a game shows 29.6 ± 3.12 minutes in a single game needs 36.3 ± 6.02 minutes in a double game.

Current insights into inherited bone marrow failure syndromes

정낙균,김명신 대한소아청소년과학회 2014 Clinical and Experimental Pediatrics (CEP) Vol.57 No.8

Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex groupof genetic disorders characterized by physical malformations, insufficient blood cell production,and increased risk of malignancies. They often have substantial phenotype overlap, and therefore,genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSshave identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosomebiogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamondsyndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genesencoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenitalneutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconianemia. Early and adequate genetic diagnosis is required for proper management and follow-upin clinical practice. Recent advances using new molecular technologies, including next generationsequencing (NGS), have helped identify new candidate genes associated with the development of bonemarrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for useas a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In thisreview, we have described recent insights into IBMFS and how they are advancing our understandingof the disease’s pathophysiology; we have also discussed the possible implications they will have inclinical practice for Korean patients.

무균성뇌막염의 임상적 고찰

구현정,정낙균,이순주,오창규,양만규 최신의학사 1993 最新醫學 Vol.36 No.7

The treatment of pediatric chronic myelogenous leukemia in the imatinib era

이재욱,정낙균 대한소아청소년과학회 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.3

Childhood chronic myelogenous leukemia (CML) is a rare hematologic disease, with limited literature on the methods of treatment. Previously,allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment for this disease. Treatment with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase (TKI), has resulted in prolonged molecular response with limited drug toxicity. Imatinib is now implemented in the primary treatment regimen for children, but the paucity of evidence on its ability to result in permanent cure and the potential complications that may arise from long-term treatment with TKIs have prevented imatinib from superseding HSCT as the primary means of curative treatment in children. The results of allogeneic HSCT in children with CML are similar to those observed in adults; HSCT-related complications such as transplant-related mortality and graft-versus-host disease remain significant challenges. An overall consensus has been formed with regards to the need for HSCT in patients with imatinib resistance or those with advanced-phase disease. However, issues such as when to undertake HSCT in chronic-phase CML patients or how best to treat patients who have relapsed after HSCT are still controversial. The imatinib era calls for a reevaluation of the role of HSCT in the treatment of CML. Specific guidelines for the treatment of pediatric CML have not yet been formulated, underscoring the importance of prospective studies on issues such as duration of imatinib treatment, optimal timing of HSCT and the type of conditioning utilized, possible treatment preand post-HSCT, and the role of second-generation TKIs.

소아 호흡기 환자에서 경구 투여된 Formoterol이 Theophyline의 혈중농도에 미치는 영향의 연구

장진경,정낙균,이숙향,조혜경 한국임상약학회 2000 한국임상약학회지 Vol.10 No.1

기관기관지 1 례

최정아,정낙균,김현희,이준성 대한소아알레르기호흡기학회 1997 Supplement Vol.7 No.2

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