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Exploring UBA1 Dysfunction in VEXAS Syndrome and Cancer
FOR IMMEDIATE RELEASE 2024-10-03
“Ultimately, a thorough grasp of the pathogenesis of VEXAS, from genetic mutations to clinical manifestations, will be pivotal in devising safe and effective therapeutic strategies to fight this challenging disease.”
As highlighted in the abstract of this paper, UBA1 is an X-linked gene that encodes one of the only two ubiquitin E1 enzymes and plays a pivotal role in initiating one of the most essential post-translational modifications. In late 2020, partial loss-of-function mutations in UBA1 within hematopoietic stem and progenitor cells were found to be responsible for VEXAS Syndrome, a previously unidentified hematoinflammatory disorder that predominantly affects older males. This condition is characterized by severe inflammation, cytopenias, and an association with hematologic malignancies.
In their paper, researchers Maki Sakuma, Torsten Haferlach, and Wencke Walter from MLL Munich Leukemia Laboratory and the Medical Graduate Center at Technical University Munich comprehensively review the molecular significance of UBA1 loss of function, along with advancements in VEXAS research over the past four years. The review covers each of the VEXAS manifestations, including inflammation, cytopenias, clonality, and potential oncogenicity.
They also explore the therapeutic landscape for VEXAS Syndrome, and detail the efficacy and potential of clone-targeting drugs based on the pathobiology of VEXAS.
“Ultimately, a thorough grasp of the pathogenesis of VEXAS, from genetic mutations to clinical manifestations, will be pivotal in devising safe and effective therapeutic strategies to fight this challenging disease.”
Correspondence to: Wencke Walter - [email protected] Keywords: cancer, VEXAS, MDS, clonal cytopenia, ubiquitin, inflammation
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About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Oncotarget is indexed and archived byPubMed/Medline,PubMed Central,Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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