This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Coombs CC, Tallman MS, Levine RL. Molecular therapy for acute myeloid leukaemia. Nat Rev Clin Oncol. 2016;13:305–18.
Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5:738–43.
Essers MA, Trumpp A. Targeting leukemic stem cells by breaking their dormancy. Mol Oncol. 2010;4:443–50.
Khoo KH, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014;13:217–36.
Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9:701–13.
Rücker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119:2114–21.
Prokocimer M, Molchadsky A, Rotter V. Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy. Blood. 2017;130:699–712.
Liu Y, Elf SE, Miyata Y, Sashida G, Liu YH, Huang G, et al. p53 Regulates Hematopoietic Stem Cell Quiescence. Cell Stem Cell. 2009;4:37–48.
Song H, Hollstein M, Xu Y. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol. 2007;15:376–88.
Chen S, Gao R, Yao C, Kobayashi M, Liu SZ, Yoder MC, et al. Genotoxic stresses promotes the clonal expansion of hematopoietic stem cells expressing mutant p53. Leukemia. 2018;32:850–4.
Garg M, Nagata Y, Kanojia D, Mayakonda A, Yoshida K, Haridas Keloth S, et al. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. Blood. 2015;126:2491–501.
Swords R, Freeman C, Giles F. Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia. Leukemia. 2012;26:2176–85.
Lee BH, Tothova Z, Levine RL, Anderson K, Buza-Vidas N, Cullen DE, et al. FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell. 2007;12:367–80.
Morse HC 3rd, Anver MR, Fredrickson TN, Haines DC, Harris AW, Harris NL, Hematopathology subcommittee of the Mouse Models of Human Cancers Consortium. et al. Bethesda proposals for classification of lymphoid neoplasms in mice. Blood. 2002;100:246–58.
Menezes J, Salgado RN, Acquadro F, Gómez-López G, Carralero MC, Barroso A, et al. ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia. Blood Cancer J. 2013;3:e157.
Acknowledgements
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Bone Marrow Failure Research Program—Idea Development Award under Award No. W81XWH-18-1-0265 to YL. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. This work was also supported in part by two NIH R56 Awards (R56DK119524-01 and R56AG05250), a DoD Career Development Award W81XWH-13-1-0187, a Scholar Award from the St. Baldrick’s Foundation, an Elsa Pardee Foundation New Investigator Award, a Leukemia Research Foundation New Investigator Award, a Showalter Trust Fund New Investigator Award, an Alex Lemonade Stand Foundation grant, a Children’s Leukemia Research Association grant, and an American Cancer Society Institutional Research Grant to YL. SCN was supported by a NIH F32 Award 1F32CA203049-01.The authors would like to acknowledge the Flow Cytometry Core and In vivo Therapeutic Core Laboratories, which were sponsored, in part, by the NIDDK Cooperative Center of Excellence in Hematology (CCEH) grant U54 DK106846. This work was supported, in part, by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108. We would like to thank Dr. Yang Xu at USCD for providing the p53R248W mice to the study.
Author contributions
SCN and YL designed the research. SCN, SC, RG, CY, MK, SV, ACF, CW, and CD performed the research. SCN, SC, and YL analyzed the data and performed the statistical analysis. GES performed pathological analysis. HSB, LDM, and RK provided reagents and constructive advice to the study. SCN, SC, and YL wrote the paper. All authors read, commented on, and approved the paper.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Nabinger, S.C., Chen, S., Gao, R. et al. Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development. Leukemia 33, 1535–1539 (2019). https://doi.org/10.1038/s41375-019-0377-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41375-019-0377-0
This article is cited by
-
Discovery and design of dual inhibitors targeting Sphk1 and Sirt1
Journal of Molecular Modeling (2023)
-
A unique role of p53 haploinsufficiency or loss in the development of acute myeloid leukemia with FLT3-ITD mutation
Leukemia (2022)
-
Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?
Stem Cell Reviews and Reports (2020)
-
Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway
Nature Communications (2019)