ArticleBlood advances2022
A new role for the SRC family kinase HCK as a driver of SYK activation in MYD88 mutated lymphomas.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Discovery of JH-XIII-05-01, a First-in-Class Dual IRAK1/IRAK4 Degrader for MYD88 Mutant Lymphomas.ACS medicinal chemistry letters · 2026Article
- Elevated FGR protein expression identifies a high-risk subset of diffuse large B-cell lymphoma and a potential therapeutic target.Frontiers in oncology · 2026Article
- A palmitoylation-related signature predicts prognosis and immune microenvironment features in diffuse large B-cell lymphoma.Frontiers in immunology · 2026Article
- HCK regulates NLRP12-mediated PANoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma.Leukemia · 2024Article
- The dual HCK/BTK inhibitor KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma.Leukemia · 2024Article
- How I use genomics and BTK inhibitors in the treatment of Waldenström macroglobulinemia.Blood · 2024Article
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
The SRC family kinase (SFK) HCK is transcriptionally upregulated and activated by mutated MYD88 (MYD88Mut), a key adaptor for Toll-receptor signaling. HCK activates BTK, AKT, and ERK in MYD88Mut lymphomas. SYK, a B-cell receptor (BCR) component, is activated in MYD88Mut lymphoma cells. Although the SFK LYN serves as a trigger for SYK activation in MYD88Mut ABC DLBCL cells, LYN activity is muted in MYD88Mut Waldenstrom macroglobulinemia (WM) cells. We therefore investigated a role for HCK in mediating SYK activation. Overexpression of wild-type (WT) (HCKWT) or gatekeeper mutated (HCKThr333Met) HCK in MYD88Mut lymphoma cells triggered SYK activation. Conversely, HCK knockdown reduced p-SYK in MYD88Mut lymphoma cells. Coimmunoprecipitation experiments showed that HCK was complexed with p-SYK in MYD88Mut BCWM.1 and TMD8 cells, but not in MYD88 WT Ramos cells. Rescue experiments in MYD88Mut lymphoma cells expressing HCKThr333Met led to persistent HCK and SYK activation and resistance to the HCK inhibitor A419259. Treatment of primary MYD88Mut WM cells with A419259 reduced p-HCK and p-SYK expression. Taken together, our findings show that SYK is activated by HCK in MYD88Mut B-cell lymphomas cells, broaden the prosurvival signaling generated by aberrant HCK expression in response to MYD88Mut, and help define HCK as an important therapeutic target in MYD88Mut B-cell lymphomas.
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