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악성 혈액질환에서 성공적인 동종골수이식 후 숙주 기질 미세환경의 구축
조상희,이제중,남찬은,최경상,정익주,이일권,김진희,박종태,김형준 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1
인체의 골수는 간엽모세포를 함유하고 있으며 이들은 골수미세환경의 주된 세포들로 분화가 가능하여 조혈기능을 지지한다. 본 연구에서는 성별이 다른 동종조혈모세포이식 환경에서 조혈모세포의 완전 생착을 보이고, 이식 후 1년에서 8년이 지난 11예의 재생불량성 빈혈 및 백혈병 환자들을 대상으로 하여 골수에서 MSC를 분리하고 체외 확장을 통해 배양된 MSC에서 X 염색체 탐식자를 이용한 FISH 및 microsatellite polymorphism PCR 기법으로 그 기원을 확인하였다. 그 결과 조혈모세포는 완전히 공여자 기원으로 대치되었음에도 불구하고 MSC는 모두 수여자 기원임을 알 수 있어, 동종조혈모세포이식에서 미세환경의 구축은 수여자의 자가 생산에 의한 골수 간질세포에 의한 것으로 생각된다. Background: Human bone marrow (BM) contains mesenchymal stem cells (MSC) that can differentiate into various cells of mesenchymal origin. It remains a matter of controversy whether donor-derived stromal cells are capable of engraftment following hematopoietic stem cell transplantation (HSCT) or not. Methods: To determine if donor-derived stromal cells are transferred to the recipients of allogeneic HSCT, we investigated the characterization of MSC in 11 patients 1 to 8 years after sex mis-matched allogeneic HSCT in severe aplastic anemia and leukemia. Results: All patients had complete engraftment with donor- derived stem cells as shown by detection of donor type DNA in peripheral blood mononuclear cells. Following culture, MSC showed the expression of SH2 and SH4, but none of the hematopoietic markers of CD14, CD34, or CD45. MSC which can be differentiated to osteogenic lineage showed the genotype of recipient completely using FISH or PCR analysis. Conclusion: This study confirmed that MSC isolated from recipients of allogeneic HSCT in severe aplastic anemia and leukemia are not of donor genotype despite of full hematopoietic engraftment with donor type. Donor cells did not contribute to reconstitute the marrow microenvironment.
( Seongjae Kim ),( Hyeoung-eun Kim ),( Boyeon Kang ),( Youn-woo Lee ),( Hangeun Kim ),( Dae Kyun Chung ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.10
Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is recognized by Toll-like receptor 2, expressed on certain mammalian cell surfaces, initiating signaling cascades that include nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase. There are many structural and functional varieties of LTA, which vary according to the different species of gram-positive bacteria that produce them. In this study, we examined whether LTA isolated from Staphylococcus aureus (aLTA) affects the expression of junction proteins in keratinocytes. In HaCaT cells, tight junctionrelated gene expression was not affected by aLTA, whereas adherens junction-related gene expression was modified. High doses of aLTA induced the phosphorylation of extracellular signal-regulated protein kinases 1 and 2, which in turn induced the epithelial-mesenchymal transition (EMT) of HaCaT cells. When cells were given a low dose of aLTA, however, NF-κB was activated and the total cell population increased. Taken together, our study suggests that LTA from S. aureus infections in the skin may contribute both to the outbreak of EMT-mediated carcinogenesis and to the genesis of wound healing in a dose-dependent manner.
선택적으로 분리된 CD34 양성 자가 조혈모세포이식 후 면역기능의 회복
이은희,김도현,정재학,박준성,김현수,홍대식,박성규,김형준,홍영선,김춘추,김효철,김원석,박찬형 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2
연구배경: 자가말초혈액 조혈모세포이식에 있어 CD34 양성세포의 선택적 분리로 인해 1~4 logs 정도의 종양세포의 감소를 가져오며, 또한 CD34 양성세포 이식 후의 면역기능의 회복은 선택적으로 분리되지 않은 자가 조혈모세포이식 시와 거의 비슷하다는 것이 보고되어 왔다. 이에 저자들은 선택적으로 분리된 자가 CD34 양성 조혈모세포이식 후의 면역기능의 회복 양상을 알아보기 위해 다기관 연구를 시행하였다. 방법: 15명의 악성 림프종, 유방암, 다발성 골수종 환자들을 대상으로 고용량 항암요법 후 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식을 시행하였다. 이식 후 1, 2, 4, 6개월에 림프구 표현형 측정과 PHA mitogen induced T세포 증식정도를 측정하였다. 결과: 이식 후 6개월 추적 관찰 시 CD3 양성, CD4 양성 림프구의 수는 정상보다 낮았고, CD8 양성세포는 정상 수준을 보였다. 초기 CD4/CD8 비는 감소되었지만 6개월 후 정상으로 회복되는 경향을 보였으며, CD19 양성, CD56 양성세포수는 정상 수준을 나타냈다. PHA mitogen response는 12개월 추적 관찰 시까지 지속적으로 증가 추세를 보였다. 결론: 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식은 빠르고 지속적인 혈액학적 생착을 유도하는 것을 알 수 있으며, 이는 기존의 연구에서 선택되지 않은 자가 조혈모세포이식 시와 비교하여 면역기능의 회복에는 유의한 차이가 없다는 보고와 일치하는 결과이다. 그러므로 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식을 통해 상당한 T 세포의 감소에도 불구하고 면역기능의 회복에 지연 없이 종양세포의 오염을 줄이는 것이 가능함을 확인하였다. Background: Positive selection of autologous peripheral blood stem cells (PBSC) for CD34-expressing cells permits 1 to 4 logs of tumor cell depletion. Hematologic recovery after CD34+ cell transplatation has been reported to be rapid and similar to results achieved in unselected autologous peripheral blood stem cell transplantation (APBSCT). We performed a multi-center study to evaluate the immune reconstitution after CD34+ immunoselected APBSCT. Methods: Fifteen patients with lymphoma, breast cancer, or multiple myeloma received high dose myeloablative chemotherapy followed by an infusion of CD34+ immunoselected PBSC. On 1, 2, 4, and 6 months after transplantation, lymphocyte phenotype was evaluated by flow cytometry and mitogen-induced T cell proliferation were measured. Results: At 6 months after transplantation, CD3+ lymphocyte subset remained below the normal range. CD4+ lymphocytes were depressed while CD8+ lymphocyte subset was in normal range. As a result, inversion of CD4/CD8 ratio was documented for first 4 months, but after 6 months follow up CD4/CD8 ratio was recovered. CD19+ B lymphocyte subset and CD56+ lymphocytes after CD34+ APBSCT were within the normal range. The PHA mitogen induced response was increased during 12 months' follow-up consistently. Phenotypic and functional reconstitution of immune cells after CD34+ cell transplantation were rapid and similar to previous studies. Conclusion: Transplantation of CD34+ immunoselected PBSC allows rapid and sustained hematologic engraftment, and there was no marked delay of immune reconstitution. The selection of CD34+ cells, although causes an extensive depletion of T lymphocytes in the graft does not represent a delayed immune recovery after transplantation.
Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A
Park, Jae Eun,Park, Byoung Chul,Kim, Hyun-A,Song, Mina,Park, Sung Goo,Lee, Do Hee,Kim, Hyeoung-Joon,Choi, Hyung-Kyoon,Kim, Jong-Tae,Cho, Sayeon Springer-Verlag 2010 Cellular and molecular life sciences Vol.67 No.15
Sang Hyuk Park,Hyun Ji Lee,In-Suk Kim,Jeong-Eun Kang,Eun Yup Lee,Hyeoung-Joon Kim,Yeo-Kyeoung Kim,Jong-Ho Won,Soo-Mee Bang,Hawk Kim,Moo-Kon Song,Joo Seop Chung,Ho Jin Shin 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.3
Background: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. Methods: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. Results: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (≤5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). Conclusions: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.