초록 ▼

Graft-versus-host diseases (GVHD)는 이식편에 포함되거나 이식편으로부터 발생한 T 세포가 공여자와는 유전적 기원이 다른 환자의 주 혹은 부 조직적합항원과 반응함으로써 발생한다. GVHD 없이도 graft-versus-malignancy (GVM) 효과가 발생한다는 사실은 공여자의 T 세포에 의해 인식되는 부 조직적합항원으로서 백혈병 세포에는 발현이 되지만 비 조혈조직에서는 발현이 되지 않는 일단의 항원이 GVHD의 표적이 됨을 시사해 준다. 본 연구자는 표준화된 STR multiplex PCR의 다년간 사용

Graft-versus-host diseases (GVHD)는 이식편에 포함되거나 이식편으로부터 발생한 T 세포가 공여자와는 유전적 기원이 다른 환자의 주 혹은 부 조직적합항원과 반응함으로써 발생한다. GVHD 없이도 graft-versus-malignancy (GVM) 효과가 발생한다는 사실은 공여자의 T 세포에 의해 인식되는 부 조직적합항원으로서 백혈병 세포에는 발현이 되지만 비 조혈조직에서는 발현이 되지 않는 일단의 항원이 GVHD의 표적이 됨을 시사해 준다. 본 연구자는 표준화된 STR multiplex PCR의 다년간 사용경험 및 그간의 조혈모세포 관련 연구를 통해 축적된 기술과 지식을 바탕으로 각종 조혈모세포 이식 후 환자의 말초혈액에서 정기적으로 T 세포를 포함한 림프구 아형을 측정하고 T 세포를 분리한 후 각 세포분획으로부터 DNA를 추출하여 세포분획 별 키메리즘을 분석하여 급성 및 만성 GVHD와의 관계를 조사하고자 하였다. 그 결과 본 연구에서는 GVHD 양상 및 질병의 재발과 관련하여 세 가지 유형의 T세포 mixed chimerism (MC)가 관찰됨을 알 수 있었다. T세포 complete chimerism (CC)는 GVHD 발생과 연관되었으며 대부분 CC에 선행하여 GVHD가 발생함도 알 수 있었다.

Abstract ▼

In recent years, increasing evidence from preciinical and early clinical pilot studies has shown that allogeneic hematopoietic stem cells can create their own space and engraft in the recipient even with nonmyeloablative or reduced toxicity conditioning regimens. After receiving such transplants, mo

In recent years, increasing evidence from preciinical and early clinical pilot studies has shown that allogeneic hematopoietic stem cells can create their own space and engraft in the recipient even with nonmyeloablative or reduced toxicity conditioning regimens. After receiving such transplants, most patients experience mixed chimerism (MC), a state of mutual tolerance between the donor and recipient. Induction of MC has the potential advantages of inhibiting graft-versus-host disease (GVHD), presumably secondary to the persistence of host immunoregulatory cells, thus allowing for later adoptive cellular immunotherapy to exploit a useful graft-versus-malignancy (GVM) effect. MC rates and kinetics are variable and dependent on the disease, the conditioning regimen, posttransplant immunosuppression, and the lineage and degrees of autologous hematopoietic recovery. Therefore, regular monitoring of chimerism is useful not only to document engraftment, graft rejection/failure, or relapse but also to provide a basis for development of new transplant protocols and interventional strategies. Furthermore, analysis of lineage-specific chimerism was found to be fundamental to improve the immunomodulation of transplant with higher sensitivity of detection. It will be important to establish defined and widely used methodologies to assess chimerism in this clinical transplantation. A comparison of MC in hematopoietic subpopulations separated by one of several methods including fluorescence activated cell sorting has been done so far mostly after myeloablative stem cell transplantation (SCT) to understand better the origin and significance of MC. Here serial post-transplant peripheral blood samples were collected from patients with various malignant diseases following myeloablative and non-myeloablative allogeneic stem cell transplantation. DNA was amplified from T-cells and polymerase chain reaction (PCR) products were quantified by an automated fluorescent DNA analyzer. All patients showed T-cell MC post-transplant, but varied in degree and duration with which complete chimerism (CC) developed, and 3 patterns emerged GVHD preceded onset of T-cell CC in the majority of the patients. Serial engraftment monitoring of T-cell chimerism status during the first 100 days after non-myeloablative stem cell transplantation is important in aiding clinical management. Molecular monitoring of chimerism is fundamental in the follow up of this group of patients. Nevertheless, standardized approaches to sample collection, timing of chimerism analysis, chimerism technology, and lineage-specific chimerism are still missing. The availability of an assay which is already validated and approved for forensic purposes may be helpful as a first step toward standardization. Unification of analysis protocols and establishment of close collaboration in the context of prospective studies should eventually allow the optimum application of interventional therapy based on chimerism results. Practical data regarding chimerism in these clinical settings are incomplete, and the type of cellular lineages, frequency of analysis, and the extent and duration of MC currently await to be further defined. It is obvious that analysis of leukocyte subsets is time consuming and can not be performed routinely. However, in high risk patients or in situations lacking other suitable disease markers, sequential chimerism analysis in leukocyte subsets permit early detection of relapse and facilitates monitoring of therapeutic intervention. For patients especially who underwent nonmyeloablative SCT, serial quantitation of at least T cell MC is fundamental to improve the immunomodulation of transplant.

목차 Contents

• 표지...1
• 목차...3
• I. 총괄현황...4
• 1. 겉표지(앞면)...5
• 2. 제출문...7
• 3. 보고서 요약서...8
• 4. 요약문(한글)...9
• 5. 요약문(영문)...11
• 6. 연구 성과 실적 및 향후 계획 ...13
• 7. 참여연구원 현황표...34
• II. 총괄연구과제 연구결과...35
• 1. 연구개발과제의 배경 및 필요성...36
• 2. 국내외 기술개발 현황...39
• 3. 연구개발과제의 추진체계...40
• 4. 연구개발수행 내용 및 결과...41
• 5. 목표달성도 및 관련분야 기여도...50
• 6. 향후 연구성과 추진계획(※해당되는 경우만 작성)...51
• 7. 연구개발결과의 파급효과...52
• 8. 연구개발결과의 활용계획...53
• 9. 연구개발과정에서 수집한 해외과학기술정보...55
• 10. 참고문헌...57
• III. 첨부서류...59
• 1. 자체평가의견서...60
• 2. 연구성과 실적 증빙서류...65