마우스 동종 조혈모세포 이식모델에서 Cyclosporin A, FK506, 3-Deazaadenosine 등의 약제가 급성 이식편대 숙주병과 생존에 미치는 영향

진종률,정대철,엄현석,정낙균,박수정,최병옥,민우성,김학기,김춘추,한치화,Jin, Jong Youl,Jeong, Dae Chul,Eom, Hyeon Seok,Chung, Nak Gyun,Park, Soo Jeong,Choi, Byung Ock,Min, Woo Sung,Kim, Hack Ki,Kim, Chun Choo,Han, Chi Wha 대한면역학회 2003 Immune Network Vol.3 No.2

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

녹색 형광단백 유전자를 함유한 아데노바이러스 주입시 마우스 생체내 발현양상

진종률(Jong Youl Jin),송치원(Chi Won Song),김진아(Jea Na Kim),이희진(Hee Jin Lee),김태규(Tai Gyu Kim),한치화(Chi Wha Han),엄현석(Hyun Seok Eom),박수정(Soo Jeong Park),정대철(Dae Chul Jeong),정낙균(Nak Gyun Chung),김소연(Soh Yeon Kim) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

N/A Background : The green fluorescent protein (GFP) from jelly fish, A equorea victoria, has become a versatile reporter for monitoring gene expression in a variety of cells and organisms . Using GFP as a marker protein we studied whether there are any differencies in the expression patterns among organs in mouse after intravenous injection of adenovirus vectors with GFP gene. Methods : Recombinant E1, E3- defective type 5 adenovirus vectors (2×10(8)/mouse) with CMV promoter and GFP gene were injected into mice via tail vein. On 3, 6, 9, 14, 21, 28 days after gene transfer, 5 mice per experiment s were sacrificed by cervical dislocation and obtained liver , lung, heart , kidney, spleen, small intestine and bone. Half of them were examined by optical microscope after H-E stain. Another half were examined by fluorescent microscope after frozen section. Western blotting were done for each samples with anti- GFP monoclonal antibody and obtained GFP bands were quantitatively compared using Gel-Doc (Bio- Rad, USA) image analyzer. Results : In all organs that we obtained, expression of GFPs are noticed 3 days after gene transfer and reached a maximum around 9th to 14th days, after then the intensities are slightly decreased but maintained until 28th days as determined by Western blotting. On fluorescent microscopic examination, GFPs are well and most frequently expressed on lung among all the examined organs. There are little expression of GFPs on liver parenchymal area around the sinusoids and central veins, although patchy expression of GFPs are observed along the liver capsules. GFPs are highly expressed around the splenic trabecula area but splenic pulp area, it is very spar sely expressed. GFPs are more frequently and highly expressed around the renal tubular area than gromerular area in kidneys. In small intestine, GFPs are expressed on mid portion of microvilli. GFPs are not expressed on myocardium except scanty expression on endocardium. Bone marrow showed GFPs but precise localization is difficult because bony spicules mashed bone marrow during the preparation of frozen section. No specific pathologic lesions possibly related with adenovirus administration are observed on microscopic examination of H-E stained specimens. Conclusions: GFPs can be detected in cells without the fixing and staining and a good marker to studying the kinetics and persistence of adenovirus mediated gene therapy. And there are different GFP expression patterns according to the organs after intravenous injection of adenovirus vectors with GFP gene in mouse.(Korean J Med 61:537- 545, 2001)

혈전성 혈소판감소성 자반증 환자에서 분리한 혈소판 응집단백 p37 은 프리트롬빈 2 와 동일하다

진종률(Jong Youl Jin),박수정(Soo Jeong Park),이종우(Jong Woo Lee),김승호(Seung Ho Kim) 대한내과학회 2001 대한내과학회지 Vol.60 No.4

N/A Background: Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread platelet thrombi with little fibrin in the arterioles and capillaries. Unusually large or multimeric von Willebrand fact or (vWF) and one or more platelet-agglutinating factors have been implicated in the pathogenesis of TTP. However, there had not been any satisfactory explanations regarding the actual mechanisms of platelet agglutination until now. Recent studies suggested 37 kDa platelet agglutinating protein (PAP p37) to be responsible for the formation of platelet thrombi in the patients with TTP. We already purified and reported 37 kDa platelet agglutinating protein (PAP p37) in a patient with TTP. To identify PAP p37, we studied more characteristics and sequenced N-terminal 21 amino acid residues of PAP p37. Methods: PAP p37 was purified from the plasma which was obtained during the first plasmapheresis in a 31-year-old male Korean patient with acute TTP by ammonium sulfate fractionation, DEAE-Sephacel, concanavalin A-Sepharose and Superose 12 gel filteration chromatographies. In each step, agglutinating activity of platelet was studied by platelet aggregometer. N-terminal 21 amino acid of PAP p37 was sequenced using automatic amino acid sequence analyzer (Beckmann, USA), Sequence Homology Analysis (NCBI BLAST 2.0 from http://www.ncbi.nlm.nih.gov/BLAST 1), and Multiple Sequence Alignment (GeneDoc 2.6.0 from http:// www.psc.edu/biomed/genedoc/). After we found out that the amino acid sequence of PAP p37 is identical with prothrombin 285- 305 amino acid sequence, prothrombin gene was sequenced by the Amersham and CircumVent thermal cycle DNA sequencing kit for detecting gene mutation. Results: The result s are as follows: 1) N-terminal 21 amino acid sequence of PAP p37 was T-F-G-S-G-E-A-D-X-G-L-R-P-L-F-E-K-K-S-L-E and appeared to be identical to that of 285- 305 amino acid residues of human prothrombin (prethrombin 2) Compared with thrombin by SDS- PAGE with or without β- mercaptoethanol, PAP p37 was suggested that is unsuccessfully cleaved thrombin light chain which was not cleaved disulfied bond between A-chain and B-chain in prethrombin 2. 2) No gene DNA mutation was found in any prothrombin gene. 3) PAP p37 revealed competitive binding against anti-thrombin antibody with thrombin by ELISA method and their antigenicity was similar with thrombin. Conclusion: PAP p37 has potent platelets agglutinating activity and the N- terminal 21 amino acid residues, the pattern of SDS-PAGE with β-mercaptoethanol and the antigenicity were the same as prethrombin 2 of procoagulant. This prethrombin 2 in TTP may develop due to unsuccessful cleaving of the thrombin light chain. These result s suggest that there are defects in procoagulant proteolysis of TTP.(Korean J Med 60:373- 382, 2001)

혈전성 혈소판 감소성 자반증에서 한국형 혈소판 응집 단백질의 분리 정제 및 특성

진종률(Jong Youl Jin),이종우(Jong Woo Lee),김승호(Seung Ho Kim) 대한내과학회 1995 대한내과학회지 Vol.48 No.1

N/A Objectives: Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread occluding and persistent microthrombotic lesions. Evidence for both endothelial damage and primary platelet aggregation as possible pathogenetic mechanisms has been produced. But the actual mechanism of platelet aggregation has not been explained satisfactorily. Recent studies suggest 37,000 mol wt plateler. aggregating protein (PAP) to be responsible for the formation of platelet thrombi in the patients with TTP. We purified and characterized a novel Korean type 37,000 mol wt platelet aggregating protein from the plasma of a patient with TTP. Methods: K-PAP was purified from the plasma which was obtained during the plasmapheresis in a 31-years- old Korean patient with TTP, by ammonium sulfate fractionation, and DEAE-Sephacel, concanavalin A-Sepharose and Superose 12 gel filtration chromatographies. In each step, platelet aggregating activity was measured by platelet aggregometer. Some biochemical characteristics were studied with PAS stain, sodium dodedyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with or without reduction and inhibition test by normal serum. Results: 1) We found a major protein band with a molecular weight of 37,000 Da and named it as K-PAP. 2) K-PAP seemed a glycoprotein with negative charge, because it bound tightly with DEAF-Sephacel and was stained by PAS. 3) The K-PAP was a single polypeptide because it runned 37,000 mol wt with or without reduction in SDS- PAGE. 4) K-PAP was not tightly bound with concanavalin A. 5) The platelet aggregating activity of K-PAP was inhibited by normal human plasma. Conclusion: In our study, a nouel K-PAP was purifide as a 37,000 mol wt glycoprotein with high platelets aggregating activity from a patient with TTP. It has similar characteistics except the weak binding activity in concanavalin A-Sepharose compared with the purified PAP in foreign reports.

몇가지 관해유도요법제에 의한 급성임파구성 백혈병의 관해율

강진형(Jin Hyoung Kang),진종률(Jong Youl Jin),홍영선(Young Seon Hong),한치화(Chi Wha Han),박종원(Jong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim),김학기(Hack Ki Kim) 대한내과학회 1987 대한내과학회지 Vol.32 No.5

N/A The case analysis of 74 patients, who were admitted to St. Mary's hospital from Jan, 1982 to Dec. 1986, and had a diagnosis as acute lymphocytic leukemia by bone marrow aspiration and biopsy was conducted. Of all the patients, the number of patients who were treated with VP regimens were 7, VPM regimens 6, VP, L-asp. regimens 4, L2, regimens 28, Modified L, regimens 15, miscellaneous regimens 3 for induction of complete remission. All of them were 63. We could find several interesting informations about the CR rate, duration of CR, survival rate between several prognostic factors. The CR rate in VP regimens was 42.9%, VP. L-asp. regimens 60.7%, L, regimens 67.9%, Modified L, regimen 93.3% According to the FAB classification, there were no difference in CR rate. (L1 76.2%, L2 70.3%, L3 80%) In patients who had CHOP regimen as consolidation, median, duration of CR was longer (6.6 months) than that in patients without CHOP (3.8 months). In the comparison of duration of survival between the immunologic classification, median duration of survival in C-ALL was 12 months and T-ALL was 4.5 months. We might come to conclusion as follows; 1) Modified L2 regimen is superior to other regimens to bring CR. 2) Early consolidation therapy give us more longterm disease free survival. 3) The survival rate of C-ALL is better than that of T-ALL.

BH - AC ( N4 - Behenoyl - 1 - β - D Arbinofuranosylcytosine ) 가 포함된 복합화학요법에 의한 급성 골수성 백혈병의 관해유도

이종욱(Jong Wook Lee),최성호(Seung Ho Choi),진종률(Jong Youl Jin),한치화(Chi Wha Han),민우성(Woo Sung Min),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim) 대한내과학회 1990 대한내과학회지 Vol.39 No.5

N/A During the last decade, there has been substantial progress in the treatment of acute myelogenaus leukemia (AML) due to the advent of multi-drug combination chemotherapy and bone marrow transplantation. N4-Behenoyl-l-β-D arabinofuranosylcytosine (BHAC) is one of the Ara-C derivatives which has been found to possess strong antitumor activity regardless of administration schedules mainly because of its resistance to cytidine deaminase. Twenty-five previously untreated adult patients with AML (Group 1) and 10 relapsed or refractory patients with AML (Group 2) were treated with BHAC containing regimens for remission induction. Thirteen patients (52%) achieved complete remission (CR) in Group 1 and 3 patients (30%) in Group 2. The median durtion of CR was 6 months (4-22). All patients whose bone marrow on the 7th day of treatment course contained no blast cell (M0) or who were below 5% blast cells (M1) entered into CR, whereas those above 25% blast cells (M3) did not enter into CR. During induction chemotherapy, 3 patients died of sepsis due to perianal abscess (1) and CVA (1) in Group 1, and of acute fulminant hepatitis (1) in Group 2 before recovery of pancytopenia. Major toxicities and side effects were as follows: infection 31/32 (96.9%), nausa and vomiting 10/32 (31. 3%), stomatitis and oral ulcer 8/32 (25%), abnormal liver function test 4/32 (12,5%), and diarrhea 3/32 (9, 4%). Rut these could be circumvented by appropriate supportive care. Even if the duration of observation doesn`t seem to be enough to compare the remission rate of BHAC-containing regimens with that of other conventional inductive regimens, this study suggests that BHAC is as effective as Ara-C for remission induction of AML. Since we expect that the higher CR rate could be obtained by escalating the dose of BHAC, further clinical trials including multicenter studies are necessary to raise the CR rate.

위선암 환자의 말초혈액에서 역전사 중합효소 연쇄반응을 이용한 Cytokeratin 20 양성 미세 전이 암세포의 진단

이승훈(Seung Hoon Lee),진종률(Jong Youl Jin),송치원(Chi Won Song),이희진(Hee Jin Lee),박재후(Jae Hoo Park),박영세(Young Se Park),백창렬(Chang Nyol Paik),우영식(Yeong Sik Woo),김희정,김춘추(Chun Choo Kim),이준욱(Joon Wook Lee) 대한내과학회 2001 대한내과학회지 Vol.60 No.6

N/A Background : The development of metastasis in cancer is one of the main problems after primary tumor resection. The identification of metastases is only possible in the follow-up investigation when there is already a solid tumor mass. Subclinical tumor cell dissemination can be detected by immunocytological staining of cells or by other molecular biological methods, like PCR. We investigated 22 peripheral blood isolates from gastric cancer patients with a cytokeratin (CK) 20 specific nested reverse transcriptase PCR (RT-PCR) for the detection of disseminated tumor cells at the time of diagnosis. Methods : Fresh heparinized peripheral bloods (about 10 mL) were obtained from 22 gastric cancer patients and 10 healthy doctors as controls. Nucleated cells were isolated by a density gradient method. RNA was isolated and then subjected to RT-PCR with CK 20 specific primers. Results : In gastric cancer, 3 of 22 (13.6%) peripheral blood isolates yielded a CK 20 mRNA positive result in a stage undependent manner. Conclusion : We detected disseminated tumor cells in the peripheral blood isolated using CK 20 specific nested RT-PCR method. Studies on a larger scale are needed for further investigation on the relationship between positive rates of CK 20 mRNA and survival rates of stomach cancer, according to cancer stages.(Korean J Med 60:514-520, 2001)

Eugenol과 1α,25-dihydroxyvitamin D₃의 병합처리에 의한 HL-60 세포의 분화 유도

오미경,박선주,김남훈,조진경,진종률,김인숙,Oh, Mi-Kyung,Park, Seon-Joo,Kim, Nam-Hoon,Cho, Jin-Kyung,Jin, Jong-Youl,Kim, In-Sook Korean Society of Life Science 2007 생명과학회지 Vol.17 No.9

Eugenol은 여러가지 향신료에 있는 필수 오일의 주요 성분으로서 악성 종양 세포의 성장을 저해하고 사멸을 유도한다고 보고되었다. 본 연구에서는 eugenol이 세포 분화 유도에 관여하는지를 조사하기 위하여 HL-60 전골 수성 백혈병 세포의 분화에 미치는 eugenol의 효과를 연구하였다. HL-60 세포에 eugenol (150 ${\mu}M$)을 가했을 때 세포성장이 저해되었으며 $1,25(OH)_{2}$ vit $D_{3}$ (3 nM)와 병합처리시에는 더 큰 저해효과를 보였다. 이 때, eugenol은 $1,25(OH)_{2}$ vit $D_{3}$에 의해 유도되는 세포주기의 $G_{0}/G_{1}$단계 정지를 더욱 증가시킴을 알 수 있었다. 또한, eugenol과 $1,25(OH)_{2}$ vit $D_{3}$를 병합처리 하였을 때에는 $G_{0}/G_{1}$단계의 정지와 관련된 세포주기 조절인자인 p27 level를 상호 협동적으로 증가시켰을 뿐만 아니라 cyclin A, cdk2, cdk4 level를 감소시켰다. 또한 유세포분석실험을 통하여, CD14 (단핵세포 표지 인자)의 발현이 eugenol과 $1,25(OH)_{2}$ vit $D_{3}$를 병합처리한 세포에서 단독처리시보다 더 증가함을 알 수 있었다. 이러한 결과들은 eugenol이 $1,25(OH)_{2}$ vit $D_{3}$와 상호협동적으로 작용하여 저농도의 $1,25(OH)_{2}$ vit $D_{3}$에 의해 자극된 세포 분화 신호를 더욱 더 증대 시킴을 나타낸다. 이러한 eugenol에 의한 세포 분화 유도 작용은 암의 화학적예방 효과에 유용하게 응용될 수 있을 것으로 기대된다. Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$ $D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$ $D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.

증례 : 내분비-대사 ; 기능성 재발을 보인 알도스테론 분비성 부신피질암 1예

문형일 ( Hyung Il Moon ),김지은 ( Ji Eun Kim ),이성수 ( Seong Su Lee ),진종률 ( Jong Youl Jin ),박일영 ( Il Young Park ),강성구 ( Sung Koo Kang ),유순집 ( Soon Jib Yoo ) 대한내과학회 2009 대한내과학회지 Vol.77 No.5S

알도스테론 분비성 부신피질암은 1955년 이후 현재까지 60여 명 보고된 매우 드문 암이다. 현재까지의 보고에 의하면 치료하지 않은 경우 평균생존율이 3개월이며 임상경과 중 전이가 흔하게 보고되어 예후가 불량한 암이다. 저자들은 반복되는 재발과 전이를 보이는 알도스테론 분비성 부신피질암 1예를 경험하였다. 내원 10개월 전 타병원에서 복강경하 알도스테론 분비성 부신피질암을 수술받은 27세 여성이 조절되지 않는 고혈압을 주소로 내원하였다. 이에 알도스테론 분비성 부신피질암의 기능성 재발로 진단하고 개복수술과 항암치료를 시행하였으며 이후에도 전이성 병변을 보여, 재수술과 방사선 치료를 시행하였다. 부신피질암의 가장 효과적인 치료는 근치적 절제이며 이것이 예후에 가장 중요한 인자이다. 이는 절제가능한 병변뿐만 아니라 재발 또는 전이성 병변에 있어서도 완전절제가 예후에 중요하다. 저자들은 젊은 환자에서 고혈압 진단에 있어서 반드시 2차성 고혈압의 진단을 유념해야 하고, 드물지만 악성 부신피질암의 가능성을 염두에 두고 이에 대한 정확한 진단과 적극적인 치료의 중요성을 강조하기 위하여 본 증례를 보고하는 바이다. Aldosterone-producing adrenocortical carcinoma (APAC) is an extremely rare disease. Recently, we experienced a case of recurrent and metastatic APAC: 10 months ago a 27-year-old female was admitted for uncontrolled hypertension after laparoscopic right adrenalectomy due to APAC. A radical operation and chemotherapy had previously been performed based on the diagnosis of APAC with functional recurrence. One-year later, metastasis to the right psoas muscle occurred, which required extensive excision and radiation therapy. Radical surgery is the only curative approach for APAC and is recommended for all patients with resectable tumors, even those with recurrent disease. Here we report a case of functional APAC (aldosterone-producing) that presented with recurrence and metastasis. (Korean J Med 77:S1206-S1211, 2009)

All - trans Retinoic Acid 가 급성전골수성백혈병의 관해유도와 혈액응고장애에 미치는 효과

김성권(Sung Gwon Kim),한치화(Chi Wha Han),김유진(Yoo Jin Kim),김동욱(Dong Wook Kim),진종률(Jong Youl Jin),민우성(Woo Sung Min),박종원(Chong Won Park),김춘추(Choon Choo Kim),김동집(Dong Jip Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.2

N/A Objectives: APL, which characteristically shows t(15:17), accompanies fatal coagulopathy during remission induction with systemic chemotherapy alone. ATRA, a derivative of vitamin A, can differentiate APL cells as well as HL-60 cells in vitro and induce higher rate of complete remission(CR). Hence, we assessed the effect of ATRA on remission induction and coagulopathy in APL patients. Methods: (1) 42 patients diagnosed histologically in St. mary's hospital from June 1991 to June 1994 were included. (2) We compared the CR rate, the time required for restoration of derranged coagulation profiles, and the amount of coagulation factors including platelets among the chemotherapy group (control) and ATRA group. Results: 1) There was no difference in CR rate between the control group and ATRA group [84.2%(16 out of 19) vs 87.0%(20 out of 23), p>0.05)] and also no difference between two subgroups of ATRA [ATRA with chemotherapy; 83.3%(10 out of 12) vs ATRA without chemotherapy; 90.9%(10 out of 11), p>0.05] 2) In the ATRA group, the CR rate of newly diagnosed patients was 82.4%(14 out of 17). The first relapsed patients (4) and the second (2) were all achieved CR. 3) The mean duration of coagulopathy, time to normalization of PT, aPTT, FDP, fibrinogen level, was 12.0±10.4, 11.1±10.2, 16.5±9.3, 15.4±10.2 days after chemotherapy alone and 4.5±4.4, 3.7±3.7, 8.9±6.1, 8.1±6.5 days in the ATRA group(p<0.05). The amount of fresh frozen plasma used in the ATRA group for the purpose of correction of coagulopathy were significantly lower than the control group(p<0.05). The incidence of profound coagulopathy during the remission induction treatment in the ATRA group was significantly lower than the control group[40% (8 out of 20) vs 96.7%(13 out of 15), p<D.05]. And the amount of platelet transfusion was not different between two groups. 4) During the treatment with ATRA, four patients showed leukocytosis, but no patient developed typical retinoic acid syndrome. Other toxicities attributable to ATRA were headache in one case, increase in transaminase in one case, bone pain in one case. These side effects were mostly short-term and easily controlled by appropriate symptomatic therapy. Conclusion: (1) ATRA is relatively safe drug for inducing CR in patients with APL who are diagnosed freshly and even in relapse. (2) Also it is effective for reducing the severity of coagulopathy associated with APL itself.