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HOXA9 has the hallmarks of a biological switch with implications in blood cancers

Author

Listed:
  • Laure Talarmain

    (Peter MacCallum Cancer Centre)

  • Matthew A. Clarke

    (University College London, Paul O’Gorman Building)

  • David Shorthouse

    (University College London)

  • Lilia Cabrera-Cosme

    (University of York)

  • David G. Kent

    (University of York)

  • Jasmin Fisher

    (University College London, Paul O’Gorman Building)

  • Benjamin A. Hall

    (University College London)

Abstract

Blood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we highlight the biological switch and prognosis marker properties of HOXA9 in AML and chronic myeloproliferative neoplasms (MPN). First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases.

Suggested Citation

  • Laure Talarmain & Matthew A. Clarke & David Shorthouse & Lilia Cabrera-Cosme & David G. Kent & Jasmin Fisher & Benjamin A. Hall, 2022. "HOXA9 has the hallmarks of a biological switch with implications in blood cancers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33189-w
    DOI: 10.1038/s41467-022-33189-w
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    References listed on IDEAS

    as
    1. Michael T. Bocker & Francesca Tuorto & Günter Raddatz & Tanja Musch & Feng-Chun Yang & Mingjiang Xu & Frank Lyko & Achim Breiling, 2012. "Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    2. Wen Xiong & James E. Ferrell, 2003. "A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision," Nature, Nature, vol. 426(6965), pages 460-465, November.
    3. Apostolos Klinakis & Camille Lobry & Omar Abdel-Wahab & Philmo Oh & Hiroshi Haeno & Silvia Buonamici & Inge van De Walle & Severine Cathelin & Thomas Trimarchi & Elisa Araldi & Cynthia Liu & Sherif Ib, 2011. "A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia," Nature, Nature, vol. 473(7346), pages 230-233, May.
    4. Jose Ameijeiras-Alonso & Rosa M. Crujeiras & Alberto Rodríguez-Casal, 2019. "Mode testing, critical bandwidth and excess mass," TEST: An Official Journal of the Spanish Society of Statistics and Operations Research, Springer;Sociedad de Estadística e Investigación Operativa, vol. 28(3), pages 900-919, September.
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