PXD066205

PXD066205 is an original dataset announced via ProteomeXchange.

Title	The histone modifier KANSL2 is an actionable biomarker for response to epigenetic modifiers in multiple myeloma
Description	Epigenetic aberrations are key drivers of multiple myeloma (MM), yet targeted therapies exploiting epigenetic alterations have not been established. By integrating clinical and molecular MM patient data sets with an unbiased genetic in vivoscreen, we identified KAT8 regulatory NSL complex subunit 2 (KANSL2) as a histone posttranslational modification (PTM)-associated candidate oncogene. High expression of KANSL2 was associated with adverse prognosis in MM patients. Genetic gain and loss of function models identified a protective role of KANSL2 towards genotoxic stress. By transcriptomics, proteomics and quantitative acetylome profiling, we identified a KANSL2-dependent specific molecular program targetable by acetylation-related modifiers. High KANSL2 levels increased sensitivity to the histone deacetylase (HDAC) inhibitor panobinostat and bromodomain and extra-terminal motif (BET) inhibitor OTX-015 and their combination. Ex vivo drug response profiling revealed that high KANSL2 expression enhances sensitivity to HDAC and BET inhibitors in primary MM patient samples. Collectively, these findings position KANSL2 as a mediator of chemotherapy resistance and actionable biomarker for response to epigenetic regulators.
HostingRepository	PRIDE
AnnounceDate	2026-02-22
AnnouncementXML	Submission_2026-02-22_11:55:00.421.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 04:25:26	ID requested
⏵ 1	2026-02-22 11:55:01	announced

10.1158/1535-7163.mct-25-0379;

Jiang K, Kirchner M, Herzberg F, Zhao Y, Gasper A, Baumgartner F, Jung P, Braune J, Schulze V, Isaakidis K, Mertins P, Kr, ö, nke J, Wirth M, Keller U, Habringer S, The histone modifier KANSL2 is an actionable biomarker in multiple myeloma. Mol Cancer Ther, ():(2025) [pubmed]

submitter keyword: histone acetylation, HDAC inhibitors, KANSL2, BET inhibitors, biomarker,Multiple Myeloma

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charite - Universitaetsmedizin Berlin and Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany
contact email	Philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
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/2026/02/PXD066205

PRIDE project URI

• PRIDE
  1. PXD066205
     1. Label: PRIDE project
     2. Name: The histone modifier KANSL2 is an actionable biomarker for response to epigenetic modifiers in multiple myeloma