IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46134-w.html
   My bibliography  Save this article

Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting

Author

Listed:
  • Yasuo Kubota

    (Taussig Cancer Institute, Cleveland Clinic)

  • Xiaorong Gu

    (Taussig Cancer Institute, Cleveland Clinic)

  • Laila Terkawi

    (Taussig Cancer Institute, Cleveland Clinic)

  • Juraj Bodo

    (Cleveland Clinic)

  • Bartlomiej P. Przychodzen

    (Taussig Cancer Institute, Cleveland Clinic)

  • Hussein Awada

    (Taussig Cancer Institute, Cleveland Clinic)

  • Nakisha Williams

    (Taussig Cancer Institute, Cleveland Clinic)

  • Carmelo Gurnari

    (Taussig Cancer Institute, Cleveland Clinic
    University of Rome Tor Vergata)

  • Naomi Kawashima

    (Taussig Cancer Institute, Cleveland Clinic)

  • Mai Aly

    (Taussig Cancer Institute, Cleveland Clinic)

  • Arda Durmaz

    (Taussig Cancer Institute, Cleveland Clinic)

  • Minako Mori

    (Taussig Cancer Institute, Cleveland Clinic)

  • Ben Ponvilawan

    (Taussig Cancer Institute, Cleveland Clinic)

  • Tariq Kewan

    (Taussig Cancer Institute, Cleveland Clinic)

  • Waled Bahaj

    (Taussig Cancer Institute, Cleveland Clinic)

  • Manja Meggendorfer

    (MLL Munich Leukemia Laboratory)

  • Babal K. Jha

    (Taussig Cancer Institute, Cleveland Clinic
    Lerner Research Institute (LRI) Cleveland Clinic)

  • Valeria Visconte

    (Taussig Cancer Institute, Cleveland Clinic)

  • Heesun J. Rogers

    (Cleveland Clinic)

  • Torsten Haferlach

    (MLL Munich Leukemia Laboratory)

  • Jaroslaw P. Maciejewski

    (Taussig Cancer Institute, Cleveland Clinic)

Abstract

PHF6 mutations (PHF6MT) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Here we show three main findings in our comprehensive genomic and proteomic study. Firstly, we show a different pattern of genes correlating with PHF6MT in male and female cases. When analyzing male and female cases separately, in only male cases, RUNX1 and U2AF1 are co-mutated with PHF6. In contrast, female cases reveal co-occurrence of ASXL1 mutations and X-chromosome deletions with PHF6MT. Next, proteomics analysis reveals a direct interaction between PHF6 and RUNX1. Both proteins co-localize in active enhancer regions that define the context of lineage differentiation. Finally, we demonstrate a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival are additive as PHF6MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type.

Suggested Citation

  • Yasuo Kubota & Xiaorong Gu & Laila Terkawi & Juraj Bodo & Bartlomiej P. Przychodzen & Hussein Awada & Nakisha Williams & Carmelo Gurnari & Naomi Kawashima & Mai Aly & Arda Durmaz & Minako Mori & Ben P, 2024. "Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46134-w
    DOI: 10.1038/s41467-024-46134-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46134-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46134-w?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. Jeffrey W. Tyner & Cristina E. Tognon & Daniel Bottomly & Beth Wilmot & Stephen E. Kurtz & Samantha L. Savage & Nicola Long & Anna Reister Schultz & Elie Traer & Melissa Abel & Anupriya Agarwal & Auro, 2018. "Functional genomic landscape of acute myeloid leukaemia," Nature, Nature, vol. 562(7728), pages 526-531, October.
    Full references (including those not matched with items on IDEAS)

    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. J. McClatchy & R. Strogantsev & E. Wolfe & H. Y. Lin & M. Mohammadhosseini & B. A. Davis & C. Eden & D. Goldman & W. H. Fleming & P. Conley & G. Wu & L. Cimmino & H. Mohammed & A. Agarwal, 2023. "Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Rebecca Anderson & Lance D. Miller & Scott Isom & Jeff W. Chou & Kristin M. Pladna & Nathaniel J. Schramm & Leslie R. Ellis & Dianna S. Howard & Rupali R. Bhave & Megan Manuel & Sarah Dralle & Susan L, 2022. "Phase II trial of cytarabine and mitoxantrone with devimistat in acute myeloid leukemia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Hanlin Wang & Guanghao Luo & Xiaobei Hu & Gaoya Xu & Tao Wang & Minmin Liu & Xiaohui Qiu & Jianan Li & Jingfeng Fu & Bo Feng & Yutong Tu & Weijuan Kan & Chang Wang & Ran Xu & Yubo Zhou & Jianmin Yang , 2023. "Targeting C/EBPα overcomes primary resistance and improves the efficacy of FLT3 inhibitors in acute myeloid leukaemia," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. David Wang & Mathieu Quesnel-Vallieres & San Jewell & Moein Elzubeir & Kristen Lynch & Andrei Thomas-Tikhonenko & Yoseph Barash, 2023. "A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Matteo Maria Naldini & Gabriele Casirati & Matteo Barcella & Paola Maria Vittoria Rancoita & Andrea Cosentino & Carolina Caserta & Francesca Pavesi & Erika Zonari & Giacomo Desantis & Diego Gilioli & , 2023. "Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Mahmoud A. Bassal & Saumya E. Samaraweera & Kelly Lim & Brooks A. Benard & Sheree Bailey & Satinder Kaur & Paul Leo & John Toubia & Chloe Thompson-Peach & Tran Nguyen & Kyaw Ze Ya Maung & Debora A. Ca, 2022. "Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Mohieddin Jafari & Mehdi Mirzaie & Jie Bao & Farnaz Barneh & Shuyu Zheng & Johanna Eriksson & Caroline A. Heckman & Jing Tang, 2022. "Bipartite network models to design combination therapies in acute myeloid leukaemia," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. W. Frank Lenoir & Micaela Morgado & Peter C. DeWeirdt & Megan McLaughlin & Audrey L. Griffith & Annabel K. Sangree & Marissa N. Feeley & Nazanin Esmaeili Anvar & Eiru Kim & Lori L. Bertolet & Medina C, 2021. "Discovery of putative tumor suppressors from CRISPR screens reveals rewired lipid metabolism in acute myeloid leukemia cells," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Brooks A. Benard & Logan B. Leak & Armon Azizi & Daniel Thomas & Andrew J. Gentles & Ravindra Majeti, 2021. "Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    10. 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.
    11. Elizabeth Heyes & Anna S. Wilhelmson & Anne Wenzel & Gabriele Manhart & Thomas Eder & Mikkel B. Schuster & Edwin Rzepa & Sachin Pundhir & Teresa D’Altri & Anne-Katrine Frank & Coline Gentil & Jakob Wo, 2023. "TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Bofei Wang & Patrick K. Reville & Mhd Yousuf Yassouf & Fatima Z. Jelloul & Christopher Ly & Poonam N. Desai & Zhe Wang & Pamella Borges & Ivo Veletic & Enes Dasdemir & Jared K. Burks & Guilin Tang & S, 2024. "Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    13. Tea Pemovska & Johannes W. Bigenzahn & Ismet Srndic & Alexander Lercher & Andreas Bergthaler & Adrián César-Razquin & Felix Kartnig & Christoph Kornauth & Peter Valent & Philipp B. Staber & Giulio Sup, 2021. "Metabolic drug survey highlights cancer cell dependencies and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    14. Tariq Kewan & Arda Durmaz & Waled Bahaj & Carmelo Gurnari & Laila Terkawi & Hussein Awada & Olisaemeka D. Ogbue & Ramsha Ahmed & Simona Pagliuca & Hassan Awada & Yasuo Kubota & Minako Mori & Ben Ponvi, 2023. "Molecular patterns identify distinct subclasses of myeloid neoplasia," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    15. Jessica Ebner & Johannes Schmoellerl & Martin Piontek & Gabriele Manhart & Selina Troester & Bing Z. Carter & Heidi Neubauer & Richard Moriggl & Gergely Szakács & Johannes Zuber & Thomas Köcher & Mich, 2023. "ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Qianze Dong & Yan Xiu & Yang Wang & Christina Hodgson & Nick Borcherding & Craig Jordan & Jane Buchanan & Eric Taylor & Brett Wagner & Mariah Leidinger & Carol Holman & Dennis J. Thiele & Sean O’Brien, 2022. "HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Lina Liu & Ana Vujovic & Nandan P. Deshpande & Shashank Sathe & Govardhan Anande & He Tian Tony Chen & Joshua Xu & Mark D. Minden & Gene W. Yeo & Ashwin Unnikrishnan & Kristin J. Hope & Yu Lu, 2022. "The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors," Nature Communications, Nature, vol. 13(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:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46134-w. 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.