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Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia

Cited 7 time in webofscience Cited 0 time in scopus
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Title
Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia
Author(s)
SH Han; S-H Kim; H-J Kim; Yoonsung Lee; S-Y Choi; G Park; D-H Kim; A Lee; J Kim; J-M Choi; Y Kim; Kyungjae Myung; Hongtae Kim; D-W Kim
Publication Date
2017-07
Journal
LEUKEMIA, v.31, no.7, pp.1532 - 1539
Publisher
NATURE PUBLISHING GROUP
Abstract
Drug resistance to BCR-ABL1 tyrosine kinase inhibitor (TKI) and disease progression to blast crisis (BC) are major clinical problems 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 signalling has been highlighted as a core mechanism for chronic phase (CP)-BC progression, stem cell survival and tyrosine kinase inhibitor resistance. We also demonstrated that high expression of Cobll1 confers drug resistance to tyrosine kinase inhibitors 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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved
URI
https://pr.ibs.re.kr/handle/8788114/4061
ISSN
0887-6924
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > Journal Papers (저널논문)
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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