Talarmain, Laure;
Clarke, Matthew;
Shorthouse, David;
Cabrera-Cosme, Lilia;
Kent, David;
Fisher, Jasmin;
Hall, Benjamin;
(2022)
HOXA9 has the hallmarks of a biological switch with implications in blood cancers.
Nature Communications
, 13
, Article 5829. 10.1038/s41467-022-33189-w.
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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.
| Type: | Article |
|---|---|
| Title: | HOXA9 has the hallmarks of a biological switch with implications in blood cancers |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-022-33189-w |
| Publisher version: | https://doi.org/10.1038/s41467-022-33189-w |
| Language: | English |
| Additional information: | © 2023 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng UCL > Provost and Vice Provost Offices > UCL BEAMS UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10155436 |
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