The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Lee, Se Ryeon,Yang, Deok Hwan,Ahn, Jae Sook,Kim, Yeo Kyeoung,Lee, Je Jung,Choi, Young Jin,Shin, Ho Jin,Chung, Joo Seop,Cho, Yoon Young,Chae, Yee Soo,Kim, Jong Gwang,Sohn, Sang Kyun,Kim, Hyeoung Joon The Korean Academy of Medical Sciences 2009 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.24 No.3

<P>A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m<SUP>2</SUP>, days 1-5), cytarabine (2.0 g/m<SUP>2</SUP>, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (<I>P</I>=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.</P>

Bortezomib and melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma

Se Ryeon Lee,박용,성화정,최철원,김병수,Seok Jin Kim 대한혈액학회 2010 Blood Research Vol.45 No.3

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.

외래에서 철 결핍 빈혈로 진단된 남자 환자의 악성 종양 유병률과 연관인자

이병현 ( Byung Hyun Lee ),이재중 ( Jae Joong Lee ),심재겸 ( Jae Kyeom Sim ),김정선 ( Jung Sun Kim ),김대식 ( Dae Sik Kim ),박세종 ( Seh Jong Park ),이세련 ( Se Ryeon Lee ),박용 ( Yong Park ),최철원 ( Chul Won Choi ),김병수 ( Byun 대한내과학회 2014 대한내과학회지 Vol.87 No.1

목적: 빈혈은 전 세계적으로 가장 흔한 질환 중 하나이며 악성 종양의 중요한 표지자이다. 빈혈과 악성 종양에 관한 다양한 연구가 있으나 IDA 진단된 남자 환자를 대상으로 한 자료는 충분하지 않다. 이에 저자들은 남자 IDA 환자의 발생원인과 악성 종양의 유병률, 철분제 치료반응에 대해 조사하였고 악성 종양에 의한 IDA 환자의 특성과 악성 종양에 대한 선별 검사로 대변 잠혈 검사의 유용성에 대해 연구하였다. 방법: 2008년 3월부터 2013년 6월까지 고려대학교 구로 병원, 안암병원 혈액내과 외래에 내원하여 IDA로 진단된 남자 환자 202명을 대상으로 하여 임상적 특성과 빈혈의 원인에 대해 조사하였고, 원인에 따라 악성 종양군(Cancer, n = 24)과 악성 종양 이외의 다른 원인군(Non-cancer, n = 178)으로 분류하여 임상적 특성 및 치료반응을 후향적으로 분석하였다. 또한 대변 잠혈 검사의 악성 종양에 대한 민감도, 특이도, 양성 예측도에 대해 분석하였다. 결과: IDA의 원인 중에서 출혈이 86명(42.6%)으로 가장 많았다. 악성 종양 유병률은 11.9% (24명)였고 악성 종양의 상대 빈도는 대장직장암 14명(58.3%), 위암 7명(29.2%) 순이 었다. 연령군별로는 50세 미만 8.3% (2명), 50세 이상 91.7% (22명)였다. 악성 종양과 관련된 요인으로는 다변량 분석에서 고령(OR, 1.05; p = 0.026)과 대변 잠별 검사 양성(OR, 7.48; p = 0.001)이 확인되었다. 치료반응은 경구 철분제 투약 후 Hb 수치가 13이상 상승한 비율은 Cancer군에서 더 낮았지만 (OR, 0.49; 95% CI, 0.146-1.668; p = 0.31) 통계적으로 유의하지 않았고 경구 철분제 투약 후 평균 Hb 수치는 Cancer군에서 12.6 ± 2.2 g/dL, Non-cancer군에서 13.8 ± 1.6 g/dL로 Cancer 군에서 더 낮았고 통계적으로 유의하였다(p = 0.016). 대변 잠혈 검사의 악성 종양에 대한 민감도는 56.3%, 특이도는 81.2%, 양성 예측도는 32.1%였다. 결론: 외래에서 진단된 남자 IDA 환자에서 악성 종양의 유병률은 11.9%로 적지 않았고 이 중에서 91.7%가 50세 이상에서 진단되었으며, 악성 종양에 의한 IDA 환자들은 다른 원인에 의한 IDA에 의한 환자들에 비해 경구 철분제 치료에 대한 반응이 좋지 못하였다. 고령(50세 이상)에 대변 잠혈 검사 양성인 남자 IDA 환자에서는 악성 종양이 진단될 확률이 높으며 특히 대장암의 가능성이 높으므로 기저 질환에 대한 철저한 검사가 필요하다. Background/Aims: Despite several reports on clinical aspects of anemia and malignancy, little is known of male patients with iron-deficiency anemia (IDA) and malignancy in Korea. We examined the cause of anemia, prevalence of and factors associated with malignancy, and treatment response to iron therapy in male IDA patients. Methods: The results of 202 males with IDA seen from March 2008 to June 2013 were analyzed retrospectively. The patients were divided into two groups based on the causes of anemia: the cancer group included patients with anemia caused by malignancy and the non-cancer group included patients with anemia due to other causes. We compared the clinical characteristics and response to iron therapy between the two groups. Results: The most common cause of IDA was bleeding (42.6%). The prevalence of malignancy was 11.9%, with colorectal cancer (58.3%) being the most common. Among the cancer patients (n = 24), 22 patients (91.7%) were age 50 or older. Independent factors associated with malignancy were old age (OR, 1.05; p = 0.026) and a positive stool occult blood test (OR, 7.48; p = 0.001). The treatment response to iron therapy based on a normalized hemoglobin level was lower in the cancer group (OR, 0.49; p = 0.31), but the difference did not reach statistical significance. The treatment response based on the mean hemoglobin level was significantly lower in the cancer group (12.6 ± 2.2 vs. 13.8 ± 1.6 g/dL, p = 0.016). Conclusions: Old age and a positive stool occult blood test were independent risk factors for malignancy in male IDA patients. We recommend screening for malignancy in patients older than 50 years or with a positive stool occult blood test. (Korean J Med 2014;87:53-60)

Geographic Variation of the Mason Bee, Osmia cornifrons (Hymenoptera: Sphecoidae) Based on Mitochondrial DNA Sequence

Hwa Young Kim,Kyung Ryong Lee,Se Ryeon Kim,Mee Yeon Hong,Dong Young Kim,Sang Beom Lee,Iksoo Kim 한국응용곤충학회 2008 한국응용곤충학회 학술대회논문집 Vol.2008 No.05

The mason bee (Osmia cornifrons Radoszkowsky) is an excellent pollinator of apple. To understand geographic genetic variation of the species and relationships among populations sequenced a portion of mitochondrial COI gene, which corresponds to “DNA Barcode” region (658 bp) from 81 individuals collected over eight localities in Korea. The sequence data were used to investigate genetic diversity within populations and species, geographic variation within species, phylogeographic relationship among populations, and phylogenetic relationship among haplotypes. Summarized, overall moderate to low genetic diversity within populations and species was characteristic, concordant with the high potential to disperse of O. cornifrons in Korea. Although two populations were genetically subdivided from the remaining localities, no clear regional bias was observed. Overall, high rate of gene flow among localities and low FST was characteristic considering other relevant studies that investigated population genetic structure of other insects occurring in Korean peninsula.

Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation

Lee, Ji Yoon,Kim, MyungJoo,Heo, Hye-Ryeon,Ha, Kwon-Soo,Han, Eun-Taek,Park, Won Sun,Yang, Se-Ran,Hong, Seok-Ho Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.11

The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

POSTERS / PW-071 : REGULATION OF THE ACTIVITY OF DEOXYHYPUSINE SYNTHASE BY PHOSPHORYLATION

(Kee Ryeon Kang),(Myung Hee Park),(So Young Lee),(Soo Ill Chung),(Choong Won Kim),(Yeon Woong Kim),(Yoon Se Kang) 한국생화학분자생물학회 (구 한국생화학회) 1999 6th IUBMB SEOUL CONFERENCE Vol.- No.-

CH₄/CO₂ GAS SEPARATION BEHAVIOR BASED ON EFFECT OF THERMAL FLUORINATION ONCARBON MOLECULAR SIEVES

Hye-Ryeon Yu,Se Ho Cho,Byong Chol Bai,Kwang Bok Yi,Young-Seak Lee 한국신재생에너지학회 2011 AFORE Vol.2011 No.-

고성능 이산화탄소 흡착용 다공성 탄소 흡착재 제조 및 그 특성

유혜련(Hye-Ryeon Yu),조세호(Se Ho Cho),김기동(Ki-Dong Kim),이교성(Kyosung Lee),이영석(Young-seak Lee) 한국신재생에너지학회 2012 한국신재생에너지학회 학술대회논문집 Vol.2012 No.06

The Efficacy of Human Placenta as a Source of the Universal Feeder in Human and Mouse Pluripotent Stem Cell Culture

Park, Yong,Lee, Seung Jin,Choi, In Young,Lee, Se Ryeon,Sung, Hwa Jung,Kim, Jong Hoon,Yoo, Young Do,Geum, Dong Ho,Kim, Sun Haeng,Kim, Byung Soo Mary Ann Liebert 2010 Cellular reprogramming Vol.12 No.3

<P>Abstract The use of a mouse embryonic fibroblast (MEF) feeder for culture of embryonic stem cells (ESCs) is a widely accepted method, regardless of the ESCs' origin and type. In this study, we performed the undifferentiated propagation of human ES cell lines (hESCs, H1, and HSF6) and mouse ES cell lines (mESCs, D3, and CE3), which were previously maintained on an MEF feeder, using human placenta-derived fibroblast-like cell (HPC) feeders originated from chorionic villi of women who had undergone therapeutic abortion due to known maternal disease that is aggravated by pregnancy. Moreover, we tried to introduce the HPC feeder for the establishment of inducible pluripotent stem cells (iPSCs) from human placental mesenchymal stem cells (MSCs). On the HPC feeder we were able to propagate ESCs and iPSCs colonies as an undifferentiated state up to the 50th passage and 20th passage, respectively. Maintenance of undifferentiated ESCs was identified by the expression of ALP, SSEA-1, SSEA-4, TRA-81, TRA-60, Oct-4, Nanog, or Rex-1. Also, addition of leukemia inhibitory factor was not required for undifferentiated propagation of mESCs on the HPC feeder. The efficiency and expression of three germ layer markers of embryoid bodies (EBs) from ESCs were satisfactory in both the MEF and HPC group. EBs formed from iPSCs were scant, and differentiation to the three germ layers was identifiable by reverst transcription-polymerase chain reactio (RT-PCR) only in the HPC group. In conclusion, the HPC feeder can efficiently support the undifferentiated propagation of hESCs, mESCs, and iPSCs, suggesting that human placenta may be a useful source of universal feeder cells for hESC, mESC, and iPSC culture.</P>

Change in serum proteome during allogeneic hematopoietic stem cell transplantation and clinical significance of serum C-reactive protein and haptoglobin

Joohyun Ryu,Se Ryeon Lee,Sung Goo Park,강성현,김형준,박병철 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.9

Successful hematopoietic stem cell transplantation (HSCT) involves the restoration of hematopoietic function after engraftment, arising from the differentiation and proliferation of hematopoietic stem cells. Several factors could influence the course of allogeneic-HSCT (allo-HSCT). Therefore, knowledge of serum proteome changes during the allo-HSCT period might increase the efficacy of diagnosis and disease prevention efforts. This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that C-reactive protein (CRP) and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown origin. Particularly, an increase in CRP level 21days after allo-HSCT was found to be an independent risk factor for MTC. Maximal haptoglobin and haptoglobin level 14 days after allo-HSCT were predictive of relapses in underlying hematologic disease. Our results indicated that CRP and haptoglobin were significantly expressed during allo-HSCT, and suggest that their level can be monitored after allo-HSCT to assess the risks of early transplant-related complications and relapse.