Dataset Information

The histone modifier KANSL2 is an actionable biomarker for response to epigenetic modifiers in multiple myeloma

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Multiple Myeloma

SUBMITTER: Marieluise Kirchner

LAB HEAD: Philipp Mertins

PROVIDER: PXD066205 | Pride | 2026-02-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Acetyl_K_Sites.txt	Txt
	Exp_design_Acetylome.txt	Txt
	Exp_design_Global_proteome.txt	Txt
	Solo_20231212_SN_HStmtpro_Habringer_G01.raw	Raw
	Solo_20231212_SN_HStmtpro_Habringer_G02.raw	Raw

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Publications

The histone modifier KANSL2 is an actionable biomarker in multiple myeloma.

Jiang Kaiting K Kirchner Marieluise M Herzberg Frederik F Zhao Yan Y Gasper Amelie A Baumgartner Francis F Jung Paul P Braune Jan J Schulze Veronika V Isaakidis Konstandina K Mertins Philipp P Krönke Jan J Wirth Matthias M Keller Ulrich U Habringer Stefan S

Molecular cancer therapeutics 20251126

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 vivo screen, 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 func ...[more]

PMID: 41294048

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