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암연구소 소개

연구실 소개

혈액암 연구실

Laboratory of Hematological malignancies
2001년 종양생물학 대학원에 참여하면서 삼성 암연구동에서 혈액암을 연구하는 실험실을 개설하였다. 내과학교실 혈액내과 소속의 김병국 교수, 윤성수 교수 및 한양대 이영렬 교수가 주도하여 혈액암 발생 및 진행 기전과 유전적 이상 및 약물 내성의 맥락에서 혈액암에 대한 연구를 진행하고자 설립되었으며, 석∙박사 대학원 과정 학생과 연구원 및 외부 기관 연구자들의 활발한 공동연구를 진행하고 있다.
참여 연구원
윤성수

윤성수 교수

  • 소속 : 내과학교실
  • 전공 : 혈액종양내과
  • 메일 : ssysmc@snu.ac.kr
  • 논문 연구실
연구내용

본 연구실은 급성골수성 백혈병, 다발 골수종 및 골수 증식성 신생물을 포함한 다양한 혈액 악성 종양에서 whole genome/exome/transcriptome sequencing과 같은 genome-wide analysis와 같은 차세대 유전체 분석 이용하여 혈액암 발생 및 진행 기전에 대해 연구를 수행하고 있다. 2012년부터 국제유전체 공동연구 consortium(ICGC: International Cancer Genome Consortium)에 참여하고 있으며 그간의 연구 성과를 Hot topic으로 선정되어 수차례 발표하였다. NGS 기술의 발전으로 single cell RNA sequencing을 통해 면역 체계에 대한 종합적인 분석이 가능해졌고, 현재 본 연구실에서는 환자 샘플을 이용하여 다양한 cell type에서 특정 cell type의 population을 파악하기 위하여 single cell RNA sequencing 분석을 수행하고, 이를 이용하여 혈액암에서 cell to cell network, cytokine profiling 등의 분석을 통해 면역 세포 네트워크 분석을 통한 바이오 마커 검출을 목표로 연구를 수행 중이다.
또한, 골수 샘플과 같은 환자 시료를 이용한 유전체 분석을 통해 발굴한 표적 유전자의 기능과 암 발생에 대한 골수 미세 환경의 역할을 조사하기 위하여 세포 수준과 동물 수준에서 실험을 수행하고 있다. 암세포 조직을 채취해 유전적 변이를 분석하고 개별적인 특징을 찾고 이를 실험용 쥐에 이식하여 Patient Derived Xenograft Model을 이용한 항암제 감수성 평가를 수행하고 있다. 이와 더불어, 유전체 분석에서 발굴한 표적 유전자가 혈액암에서 작용하는 기전을 확인하기 위하여 변이 세포주를 제작하고 표적 유전자에 따른 면역 기전 변화를 제작한 세포주에서 확인하는 연구를 수행하고 있다. 현재 혈액암에서 면역 억제제의 치료효과를 확인하기 위하여 Genentech과의 공동연구도 함께 수행 중이다.
이를 통해 연구실은 유수의 제약회사와 신약의 항암 효과를 규명하는 전(前)임상시험을 수행하고 있으며, 이렇게 개발된 신약들을 이용하여 초기 임상시험을 환자를 대상으로 진행하고 있다.

연구목표
본 연구실은 차세대 염기 서열 데이터를 이용한 유전체 분석과 환자 유래 검체들을 이용한 실험 연구를 통해 혈액암의 진행 및 재발 기전과 같은 유전적 변화를 새롭게 발견하고 이를 증명하기 위한 기전 연구 및 항암제 개발 연구의 기반을 다지는 것을 목표로 하고 있다. 이는 궁극적으로 미래 정밀 의료를 위한 혁신적인 임상 시험으로 이어질 수 있는 잠재적인 혈액암 치료 표적의 개발과 새로운 치료법 개발로 이어질 것이다.
연구성과
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● Comparison of the effect of DLI according to cell sources in relapsed AML after allogeneic stem cell transplantation. Ann Hematol. 2023 Mar;102(3):629-639
● ITDetect: a method to detect internal tandem duplication of FMS-like tyrosine kinase (FLT3) from next-generation sequencing data with high sensitivity and clinical application. BMC Bioinformatics. 2023 Feb 23;24(1):62
● Identification of novel Carnobacterium maltaromaticum strains in bone marrow samples of patients with acute myeloid leukemia using a metagenomic binning approach. Int Microbiol. 2023 Apr 22.
● Mitigating the BFL1-mediated antiapoptotic pathway in diffuse large B cell lymphoma by inhibiting HDACs. Leuk Lymphoma. 2023 Jan;64(1):205-216.
● Evaluation of Low-Molecular-Weight Heparin for Treatment of Portal Vein Thrombosis in Liver Cirrhosis Patients. Medicina (Kaunas). 2023 Feb 4;59(2):292.
● Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment. Genome Med. 2022 Sep 28;14(1):111.
● Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents. Mol Ther Nucleic Acids. 2022 Jul 21;29:370-383.
● The importance of critically short telomere in myelodysplastic syndrome. Biomark Res. 2022 Nov 10;10(1):79.
● Expansion of Human Megakaryocyte-Lineage Progeny via Aryl Hydrocarbon Receptor Antagonism with CH223191. Stem Cell Rev Rep. 2022 Dec;18(8):2982-2994.
● Increased Apoptotic Activity in Low-Risk Myelodysplastic Syndrome. J Clin Med. 2022 Aug 7;11(15):4604.
● Cyclophosphamide addition to pomalidomide/dexamethasone is not necessarily associated with universal benefits in RRMM. PLoS One. 2022 Jan 27;17(1):e0260113.
● IDH1/2 mutations in acute myeloid leukemia. Blood Res. 2022 Mar 31;57(1):13-19.
● Characteristics of Sweet syndrome in patients with or without malignancy. Ann Hematol. 2022 Jul;101(7):1499-1508.
● Limited benefits of thalidomide and dexamethasone maintenance after autologous stem cell transplantation in newly diagnosed multiple myeloma patients: a prospective phase II multi-center study in Korea. Curr Probl Cancer. 2022 Feb;46(1):100786.
● Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs. Proc Natl Acad Sci U S A. 2021 Mar 30;118(13):e2016289118.
● Metabolic Profiling during Acute Myeloid Leukemia Progression Using Paired Clinical Bone Marrow Serum Samples. Metabolites. 2021 Aug 31;11(9):586.
● Ultradeep Sequencing Analysis of Paroxysmal Nocturnal Hemoglobinuria Clones Detected by Flow Cytometry: PIG Mutation in Small PNH Clones. Am J Clin Pathol. 2021 Jun 17;156(1):72-85.
● Incidence of invasive fungal infection in acute lymphoblastic and acute myelogenous leukemia in the era of antimold prophylaxis. Sci Rep. 2021 Nov 12;11(1):22160.
● Incidence, characteristics and risk factors of thromboembolic events in East Asian patients with BCR-ABL1 negative myeloproliferative neoplasms. Sci Rep. 2021 Sep 8;11(1):17819.
● Leukemic stem cell phenotype is associated with mutational profile in acute myeloid leukemia. Korean J Intern Med. 2021 Mar;36(2):401-412.
● Pan-RAF inhibitor LY3009120 is highly synergistic with low-dose cytarabine, but not azacitidine, in acute myeloid leukemia with RAS mutations. Oncol Lett. 2021 Nov;22(5):745.
● A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Intermediated-risk Acute Myeloid Leukemia Patients. In Vivo. 2021 Jan-Feb;35(1):617-622.
● Identification of an Optimal Population for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Mature T and NK Cell Neoplasms. In Vivo. 2021 Jul-Aug;35(4):2379-2390.
● Romiplostim plus danazol as salvage treatment for eltrombopag refractory immune thrombocytopenia: a retrospective pilot study. Blood Res. 2021 Sep 30;56(3):202-204.
● MED-TMA: A clinical decision support tool for differential diagnosis of TMA with enhanced accuracy using an ensemble method. Thromb Res. 2020 Sep;193:154-159.
● Decreased vitamin C uptake mediated by SLC2A3 promotes leukaemia progression and impedes TET2 restoration. Br J Cancer. 2020 May;122(10):1445-1452.
● Proper Read Filtering Method to Adequately Analyze Whole-Transcriptome Sequencing and RNA Based Immune Repertoire Sequencing Data for Tumor Milieu Research. Cancers (Basel). 2020 Dec 9;12(12):3693.
● Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer. Commun Biol. 2020 Oct 30;3(1):630.
● Preconditioning Absolute Lymphocyte Count and Transplantation Outcomes in Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Reduced-Intensity Conditioning and Antithymocyte Globulin Treatment. Biol Blood Marrow Transplant. 2020 Oct;26(10):1855-1860.
● Association of HSV-1 and Reduced Oral Bacteriota Diversity with Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation. J Clin Med. 2020 Apr 11;9(4):1090.
● Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial-mesenchymal transition utilizing RAF/MAPK pathway. Carcinogenesis. 2020 Jul 10;41(6):817-827.
● Limited Positive Predictive Value of β-d-Glucan in Hematologic Patients Receiving Antimold Prophylaxis. Open Forum Infect Dis. 2020 Feb 12;7(3):ofaa048.
● Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia. BMC Infect Dis. 2020 Jun 9;20(1):404.
● Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies. Korean J Intern Med. 2020 Sep;35(5):1188-1198.
● Induction of leukemic stem cell differentiation by aryl hydrocarbon receptor agonist and synergy with gilteritinib in FLT3-ITD + acute myeloid leukemia. Leuk Lymphoma. 2020 Aug;61(8):1932-1942.
● Synergistic Effect of Alectinib and Everolimus on ALK-positive Anaplastic Large Cell Lymphoma Growth Inhibition. Anticancer Res. 2020 Mar;40(3):1395-1403.
● Characterization and Prognosis of Secondary Acute Myeloid Leukemia in an Asian Population: AML With Antecedent Hematological Disease Confers Worst Outcomes, Irrespective of Cytogenetic Risk. Anticancer Res. 2020 May;40(5):2917-2924.
● Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome. Blood Res. 2020 Mar;55(1):27-34.
● Prognostic value of metabolic tumour volume on baseline 18F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI. Eur J Nucl Med Mol Imaging. 2019 Jul;46(7):1417-1427.
● Oncogenic effects of germline variants in lysosomal storage disease genes. Genet Med. 2019 Dec;21(12):2695-2705.
● Interpretation of EBV infection in pan-cancer genome considering viral life cycle: LiEB (Life cycle of Epstein-Barr virus). Sci Rep. 2019 Mar 5;9(1):3465.
● Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy. BMC Cancer. 2019 Apr 16;19(1):358.
● Comparison of quality of life and health behaviors in survivors of acute leukemia and the general population. Ann Hematol. 2019 Oct;98(10):2357-2366.
● Telomere length and its correlation with gene mutations in chronic lymphocytic leukemia in a Korean population. PLoS One. 2019 Jul 23;14(7):e0220177.
● Replicative senescence of hematopoietic cells in patients with idiopathic cytopenia of undetermined significance. Leuk Res. 2019 Apr;79:22-26.
● The upregulation of Pim kinases is essential in coordinating the survival, proliferation, and migration of KIT D816V-mutated neoplastic mast cells. Leuk Res. 2019 Aug;83:106166.
● Targeted sequencing aids in identifying clonality in chronic myelomonocytic leukemia. Leuk Res. 2019 Sep;84:106190.
● ASXL1 is a molecular predictor in idiopathic cytopenia of undetermined significance. Leuk Lymphoma. 2019 Mar;60(3):756-763.
● ERK-dependent IL-6 positive feedback loop mediates resistance against a combined treatment using danusertib and BKM120 in Burkitt lymphoma cell lines. Leuk Lymphoma. 2019 Oct;60(10):2532-2540.
● Characteristics of Waldenström Macroglobulinemia in Korean Patients According to Mutational Status of MYD88 and CXCR4: Analysis Using Ultra-Deep Sequencing. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e496-e505.
● Comparison of Different Conditioning Regimens in Allogeneic Hematopoietic Stem-Cell Transplantation Shows Superiority of Total Body Irradiation-Based Regimen for Younger Patients With Acute Leukemia: A Nationwide Study. Clin Lymphoma Myeloma Leuk. 2019 Nov;19(11):e605-e615.
● The Temporal Sequence and the Differences in Somatic Mutation Acquisition Determines Clinical Behaviors of JAK2-Positive Myeloproliferative Neoplasms. Anticancer Res. 2019 Nov;39(11):6273-6282.
● Combination of Genetic Aberration With International Staging System Classification for Stratification of Asian Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation. In Vivo. 2019 Mar-Apr;33(2):611-619.
● Plasma-based protein biomarkers can predict the risk of acute graft-versus-host disease and non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis. 2019 Feb;74:5-12.
● Differential impact of anti-thymocyte globulin dosing by disease risk index in alternative donor peripheral blood stem cell transplantation in patients with acute leukemia or myelodysplastic syndrome after reduced intensity conditioning. Blood Res. 2019 Dec;54(4):290-295.
구성원
성명 소속 직급
윤성수 서울대학교 의과대학 내과학교실 교수
고영일 서울대학교 의과대학 내과학교실 부교수
신동엽 서울대학교 의과대학 내과학교실 부교수
홍준식 서울대학교 의과대학 내과학교실 부교수
변자민 서울대학교 의과대학 내과학교실 조교수
윤홍석 서울대병원 임상유전체의학과 조교수
연구실사진
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