한빛사논문
- 조회1,839
Abstract
S H Han1,9, S-H Kim2,9, H-J Kim1,9, Y Lee3,9, S-Y Choi2, G Park4, D-H Kim5, A Lee6, J Kim6, J-M Choi5, Y Kim6, K Myung3,*, H Kim1,7,* and D-W Kim2,8,*
1Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea
2Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea
3Center for Genomic Integrity Institute for Basic Science (IBS), Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea
4Department of Pathology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
5Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea
6Department of Life Systems, Sookmyung Women’s University, Seoul, Korea
7Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)
8Department of Hematology, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
9These authors contributed equally to this work.
*Correspondence: K Myung, 50 UNIST-gil, Ulsan 689-798, Republic of Korea. Professor H Kim, Biological Sciences, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea. D-W Kim, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea.
Abstract
Drug resistance to BCR-ABL1 tyrosine kinase inhibitors (TKI) and disease progression to blast crisis (BC) are major clinical problem in chronic myeloid leukemia (CML), however underlying mechanisms governing this process remain to be elucidated. Here, we report Cordon-bleu protein-like 1 (Cobll1) as a distinct molecular marker associated with drug resistance as well as progression to BC. In detail, Cobll1 increases IKKγ stability, leading to NF-κB activation and reduction of nilotinib-dependent apoptosis, suggesting Cobll1-mediated NF-κB could be involved in drug resistance. Recently, NF-κB signaling has been highlighted as core mechanism for CP (chronic phase)-BC progression, stem cell survival and TKI resistance. We also demonstrated that high expression of Cobll1 confers drug resistance to TKIs in CML cell line as well as patient samples. The analysis of large sets of primary CML samples (n=90) shows that Cobll1 expression is dramatically increased in BC but not in CP, which is correlated with a poor survival rate (P=0.002). Moreover, our studies show that Cobll1 is highly expressed in CD34+ primitive stem cell populations, and the zebrafish paralog Cobll1b is important for normal hematopoiesis during embryonic development. Based on these results, we propose that Cobll1 is a novel biomarker and potential therapeutic target for CML-BC.
논문정보
- Research article
- 2017년 02월 (BRIC 등록일 2017-03-06)
- 국내 연구진
- 생명과학 > 분자생물학
관련 보도자료
- 사이언스엠디
- 2017. 03. 02
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