IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0039725.html
   My bibliography  Save this article

NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches

Author

Listed:
  • Wenxue Ma
  • Alejandro Gutierrez
  • Daniel J Goff
  • Ifat Geron
  • Anil Sadarangani
  • Christina A M Jamieson
  • Angela C Court
  • Alice Y Shih
  • Qingfei Jiang
  • Christina C Wu
  • Kang Li
  • Kristen M Smith
  • Leslie A Crews
  • Neil W Gibson
  • Ida Deichaite
  • Sheldon R Morris
  • Ping Wei
  • Dennis A Carson
  • A Thomas Look
  • Catriona H M Jamieson

Abstract

Background: Leukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL) and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated. Methodology and Principal Findings: We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34+ cells from NOTCH1Mutated T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1Wild-type CD34+ cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1Mutated CD34+ fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1Mutated T-ALL LIC-engrafted mice and resulted in depletion of CD34+CD2+CD7+ cells that harbor serial transplantation capacity. Conclusions: These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies.

Suggested Citation

  • Wenxue Ma & Alejandro Gutierrez & Daniel J Goff & Ifat Geron & Anil Sadarangani & Christina A M Jamieson & Angela C Court & Alice Y Shih & Qingfei Jiang & Christina C Wu & Kang Li & Kristen M Smith & , 2012. "NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-14, June.
  • Handle: RePEc:plo:pone00:0039725
    DOI: 10.1371/journal.pone.0039725
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039725
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0039725&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0039725?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Irina M. Conboy & Michael J. Conboy & Amy J. Wagers & Eric R. Girma & Irving L. Weissman & Thomas A. Rando, 2005. "Rejuvenation of aged progenitor cells by exposure to a young systemic environment," Nature, Nature, vol. 433(7027), pages 760-764, February.
    2. Yan Wu & Carol Cain-Hom & Lisa Choy & Thijs J. Hagenbeek & Gladys P. de Leon & Yongmei Chen & David Finkle & Rayna Venook & Xiumin Wu & John Ridgway & Dorreyah Schahin-Reed & Graham J. Dow & Amy Shelt, 2010. "Therapeutic antibody targeting of individual Notch receptors," Nature, Nature, vol. 464(7291), pages 1052-1057, April.
    3. Kristina Anderson & Christoph Lutz & Frederik W. van Delft & Caroline M. Bateman & Yanping Guo & Susan M. Colman & Helena Kempski & Anthony V. Moorman & Ian Titley & John Swansbury & Lyndal Kearney & , 2011. "Genetic variegation of clonal architecture and propagating cells in leukaemia," Nature, Nature, vol. 469(7330), pages 356-361, January.
    4. Takahiro Ito & Hyog Young Kwon & Bryan Zimdahl & Kendra L. Congdon & Jordan Blum & William E. Lento & Chen Zhao & Anand Lagoo & Gareth Gerrard & Letizia Foroni & John Goldman & Harriet Goh & Soo-Hyun , 2010. "Regulation of myeloid leukaemia by the cell-fate determinant Musashi," Nature, Nature, vol. 466(7307), pages 765-768, August.
    5. Tannishtha Reya & Andrew W. Duncan & Laurie Ailles & Jos Domen & David C. Scherer & Karl Willert & Lindsay Hintz & Roel Nusse & Irving L. Weissman, 2003. "A role for Wnt signalling in self-renewal of haematopoietic stem cells," Nature, Nature, vol. 423(6938), pages 409-414, May.
    6. Marc H. G. P. Raaijmakers & Siddhartha Mukherjee & Shangqin Guo & Siyi Zhang & Tatsuya Kobayashi & Jesse A. Schoonmaker & Benjamin L. Ebert & Fatima Al-Shahrour & Robert P. Hasserjian & Edward O. Scad, 2010. "Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia," Nature, Nature, vol. 464(7290), pages 852-857, April.
    7. Raymond E. Moellering & Melanie Cornejo & Tina N. Davis & Cristina Del Bianco & Jon C. Aster & Stephen C. Blacklow & Andrew L. Kung & D. Gary Gilliland & Gregory L. Verdine & James E. Bradner, 2009. "Direct inhibition of the NOTCH transcription factor complex," Nature, Nature, vol. 462(7270), pages 182-188, November.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chahrazed Benosman & Bedr’Eddine Aïnseba & Arnaud Ducrot, 2015. "Optimization of Cytostatic Leukemia Therapy in an Advection–Reaction–Diffusion Model," Journal of Optimization Theory and Applications, Springer, vol. 167(1), pages 296-325, October.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yi-Ing Chen & Chin-Chun Chang & Min-Fen Hsu & Yung-Ming Jeng & Yu-Wen Tien & Ming-Chu Chang & Yu-Ting Chang & Chun-Mei Hu & Wen-Hwa Lee, 2022. "Homophilic ATP1A1 binding induces activin A secretion to promote EMT of tumor cells and myofibroblast activation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Tatiana Erazo & Chiara M. Evans & Daniel Zakheim & Eren L. Chu & Alice Yunsi Refermat & Zahra Asgari & Xuejing Yang & Mariana Silva Ferreira & Sanjoy Mehta & Marco Vincenzo Russo & Andrea Knezevic & X, 2022. "TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Felicia Lazure & Rick Farouni & Korin Sahinyan & Darren M. Blackburn & Aldo Hernández-Corchado & Gabrielle Perron & Tianyuan Lu & Adrien Osakwe & Jiannis Ragoussis & Colin Crist & Theodore J. Perkins , 2023. "Transcriptional reprogramming of skeletal muscle stem cells by the niche environment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Olena S. Tokareva & Kunhua Li & Tara L. Travaline & Ty M. Thomson & Jean-Marie Swiecicki & Mahmoud Moussa & Jessica D. Ramirez & Sean Litchman & Gregory L. Verdine & John H. McGee, 2023. "Recognition and reprogramming of E3 ubiquitin ligase surfaces by α-helical peptides," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Yuri Frosi & Yen-Chu Lin & Jiang Shimin & Siti Radhiah Ramlan & Kelly Hew & Alf Henrik Engman & Anil Pillai & Kit Yeung & Yue Xiang Cheng & Tobias Cornvik & Par Nordlund & Megan Goh & Dilraj Lama & Za, 2022. "Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    7. Ayşegül Erdem & Silvia Marin & Diego A. Pereira-Martins & Roldán Cortés & Alan Cunningham & Maurien G. Pruis & Bauke Boer & Fiona A. J. Heuvel & Marjan Geugien & Albertus T. J. Wierenga & Annet Z. Bro, 2022. "The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically distinct subtypes of human acute myeloid leukemia," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Michelle M. Kameda-Smith & Helen Zhu & En-Ching Luo & Yujin Suk & Agata Xella & Brian Yee & Chirayu Chokshi & Sansi Xing & Frederick Tan & Raymond G. Fox & Ashley A. Adile & David Bakhshinyan & Kevin , 2022. "Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Nikolai Schleussner & Pierre Cauchy & Vedran Franke & Maciej Giefing & Oriol Fornes & Naveen Vankadari & Salam A. Assi & Mariantonia Costanza & Marc A. Weniger & Altuna Akalin & Ioannis Anagnostopoulo, 2023. "Transcriptional reprogramming by mutated IRF4 in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Hao Wang & R. Alejandro Sica & Gurbakhash Kaur & Phillip M. Galbo & Zhixin Jing & Christopher D. Nishimura & Xiaoxin Ren & Ankit Tanwar & Bijan Etemad-Gilbertson & Britta Will & Deyou Zheng & David Fo, 2024. "TMIGD2 is an orchestrator and therapeutic target on human acute myeloid leukemia stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Rongli Sun & Juan Zhang & Mengzhen Xiong & Haiyan Wei & Kehong Tan & Lihong Yin & Yuepu Pu, 2015. "Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure," IJERPH, MDPI, vol. 12(8), pages 1-16, August.
    12. Songbai Zhang & Ayako Miyakawa & Malin Wickström & Cecilia Dyberg & Lauri Louhivuori & Manuel Varas-Godoy & Kati Kemppainen & Shigeaki Kanatani & Dagmara Kaczynska & Ivar Dehnisch Ellström & Lotta Elf, 2022. "GIT1 protects against breast cancer growth through negative regulation of Notch," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    13. Udit Singhal & Srinivas Nallandhighal & Jeffrey J. Tosoian & Kevin Hu & Trinh M. Pham & Judith Stangl-Kremser & Chia-Jen Liu & Razeen Karim & Komal R. Plouffe & Todd M. Morgan & Marcin Cieslik & Rober, 2024. "Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    14. David E. Lee & Lauren K. McKay & Akshay Bareja & Yongwu Li & Alastair Khodabukus & Nenad Bursac & Gregory A. Taylor & Gurpreet S. Baht & James P. White, 2022. "Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    15. Naomi Kawashima & Yuichi Ishikawa & Jeong Hui Kim & Yoko Ushijima & Akimi Akashi & Yohei Yamaguchi & Hikaru Hattori & Marie Nakashima & Seara Ikeno & Rika Kihara & Takahiro Nishiyama & Takanobu Morish, 2022. "Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    16. Yuxuan Liu & Zhimin Gu & Hui Cao & Pranita Kaphle & Junhua Lyu & Yuannyu Zhang & Wenhuo Hu & Stephen S. Chung & Kathryn E. Dickerson & Jian Xu, 2021. "Convergence of oncogenic cooperation at single-cell and single-gene levels drives leukemic transformation," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0039725. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.