PXD041092
PXD041092 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Exceptional Response to BTK Inhibitors in Aggressive Lymphomas Linked to Chronic Selective Autophagy |
Description | Diffuse large B cell lymphoma is an aggressive cancer type that is profoundly heterogeneous, both molecularly and phenotypically, presenting a challenge for precision medicine. Inhibitors of the kinase BTK block B cell receptor (BCR)-dependent NF-ï«B signaling and are particularly effective in certain molecular subtypes of DLBCL, but the underlying mechanisms are poorly understood. The MCD genetic subtype, which often acquires mutations targeting the BCR subunit CD79B and MYD88, typically resists chemotherapy but responds exceptionally to BTK inhibitors. By functional proteogenomics, we discovered a non-canonical form of chronic active selective autophagy in MCD DLBCL that targets ubiquitinated mutant MYD88, an adaptor protein essential for oncogenic NF-ï«B survival signaling, for degradation. Moreover, MCD tumors acquire genetic and epigenetic alterations that attenuate this novel tumor suppressive pathway. Importantly, BTK inhibitors activated this chronic selective autophagy pathway to degrade MYD88, thus explaining the exceptional benefit of BTK-targeted therapies in the MCD DLBCL subtype. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-06 |
AnnouncementXML | Submission_2025-05-06_14:25:28.879.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Sebastian Scheich |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitinylated lysine; biotinylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF; Orbitrap Exploris 480; Q Exactive; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-03-24 04:43:48 | ID requested | |
⏵ 1 | 2025-05-06 14:25:29 | announced |
Publication List
Phelan JD, Scheich S, Choi J, Wright GW, H, ä, upl B, Young RM, Rieke SA, Pape M, Ji Y, Urlaub H, Bolomsky A, Doebele C, Zindel A, Wotapek T, Kasbekar M, Collinge B, Huang DW, Coulibaly ZA, Morris VM, Zhuang X, Enssle JC, Yu X, Xu W, Yang Y, Zhao H, Wang Z, Tran AD, Shoemaker CJ, Shevchenko G, Hodson DJ, Shaffer AL, Staudt LM, Oellerich T, Response to Bruton's tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy. Cancer Cell, 42(2):238-252.e9(2024) [pubmed] |
10.1016/j.ccell.2023.12.019; |
Keyword List
submitter keyword: funtional proteogenomics,DLBCL, selective autophagy, BTK inhibition |
Contact List
Louis M. Staudt | |
---|---|
contact affiliation | Lymphoid Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda, Maryland |
contact email | lstaudt@mail.nih.gov |
lab head | |
Sebastian Scheich | |
contact affiliation | Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. |
contact email | sebastian.scheich@nih.gov |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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