PXD041092-1

PXD041092 is an original dataset announced via ProteomeXchange.

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-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-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

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-24 04:43:48	ID requested
⏵ 1	2025-05-06 14:25:29	announced

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;

submitter keyword: funtional proteogenomics,DLBCL, selective autophagy, BTK inhibition

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD041092

PRIDE project URI

• PRIDE
  1. PXD041092
     1. Label: PRIDE project
     2. Name: Exceptional Response to BTK Inhibitors in Aggressive Lymphomas Linked to Chronic Selective Autophagy