ULK1 inhibition promotes oxidative stress-induced differentiation and sensitizes leukemic stem cells to targeted therapy (Record no. 1650)
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042 ## - AUTHENTICATION CODE | |
---|---|
Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Ianniciello, Angela |
Relator term | author |
9 (RLIN) | 1022 |
245 00 - TITLE STATEMENT | |
Title | ULK1 inhibition promotes oxidative stress-induced differentiation and sensitizes leukemic stem cells to targeted therapy |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Date of publication, distribution, etc. | 2021-09-29. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7612079/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/34586834 |
520 ## - SUMMARY, ETC. | |
Summary, etc. | Inhibition of autophagy has been proposed as a potential therapy for individuals with cancer. However, current lysosomotropic autophagy inhibitors have demonstrated limited efficacy in clinical trials. Therefore, validation of novel specific autophagy inhibitors using robust preclinical models is critical. In chronic myeloid leukemia (CML), minimal residual disease is maintained by persistent leukemic stem cells (LSCs), which drive tyrosine kinase inhibitor (TKI) resistance and patient relapse. Here, we show that deletion of autophagy-inducing kinase ULK1 (unc-51-like autophagy activating kinase 1) reduces growth of cell line and patient-derived xenografted CML cells in mouse models. Using primitive cells, isolated from individuals with CML, we demonstrate that pharmacological inhibition of ULK1 selectively targets CML LSCs ex vivo and in vivo, when combined with TKI treatment. The enhanced TKI sensitivity after ULK1-mediated autophagy inhibition is driven by increased mitochondrial respiration and loss of quiescence and points to oxidative stress-induced differentiation of CML LSCs, proposing an alternative strategy for treating patients with CML. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Article |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Zarou, Martha M. |
Relator term | author |
9 (RLIN) | 1023 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Rattigan, Kevin M. |
Relator term | author |
9 (RLIN) | 1024 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Scott, Mary |
Relator term | author |
9 (RLIN) | 1025 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Dawson, Amy |
Relator term | author |
9 (RLIN) | 1026 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Dunn, Karen |
Relator term | author |
9 (RLIN) | 1027 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Brabcova, Zuzana |
Relator term | author |
9 (RLIN) | 1028 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kalkman, Eric R. |
Relator term | author |
9 (RLIN) | 1029 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Nixon, Colin |
Relator term | author |
9 (RLIN) | 1030 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Michie, Alison M. |
Relator term | author |
9 (RLIN) | 1031 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Copland, Mhairi |
Relator term | author |
9 (RLIN) | 1032 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Vetrie, David |
Relator term | author |
9 (RLIN) | 1033 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Ambler, Martin |
Relator term | author |
9 (RLIN) | 1034 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Saxty, Barbara |
Relator term | author |
9 (RLIN) | 1035 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Helgason, G. Vignir |
Relator term | author |
9 (RLIN) | 1036 |
786 0# - DATA SOURCE ENTRY | |
Note | Sci Transl Med |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1126/scitranslmed.abd5016">http://dx.doi.org/10.1126/scitranslmed.abd5016</a> |
Public note | Connect to this object online. |
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