The role of aurora A and polo-like kinases in high-risk lymphomas

High-risk lymphomas (HRLs) are associated with dismal outcomes and remain a therapeutic challenge. Recurrent genetic and molecular alterations, including c-myc expression and aurora A kinase (AAK) and polo-like kinase-1 (PLK1) activation, promote cell proliferation and contribute to the highly aggre...

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Veröffentlicht in:Blood advances 2019-06, Vol.3 (11), p.1778-1787
Hauptverfasser: Murga-Zamalloa, Carlos, Inamdar, Kedar V., Wilcox, Ryan A.
Format: Artikel
Sprache:eng
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Zusammenfassung:High-risk lymphomas (HRLs) are associated with dismal outcomes and remain a therapeutic challenge. Recurrent genetic and molecular alterations, including c-myc expression and aurora A kinase (AAK) and polo-like kinase-1 (PLK1) activation, promote cell proliferation and contribute to the highly aggressive natural history associated with these lymphoproliferative disorders. In addition to its canonical targets regulating mitosis, the AAK/PLK1 axis directly regulates noncanonical targets, including c-myc. Recent studies demonstrate that HRLs, including T-cell lymphomas and many highly aggressive B-cell lymphomas, are dependent upon the AAK/PLK1 axis. Therefore, the AAK/PLK1 axis has emerged as an attractive therapeutic target in these lymphomas. In addition to reviewing these recent findings, we summarize the rationale for targeting AAK/PLK1 in high-risk and c-myc–driven lymphoproliferative disorders. [Display omitted]
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2019000232