Research Papers:
NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma
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Abstract
Andrea Gunnell1, Scott T. Kimber1,2, Richard Houlston1 and Martin Kaiser1
1 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK
2 Present address: Camallergy, Gosport, Hampshire, PO13 0AU, UK
Correspondence to:
| Andrea Gunnell, | email: | [email protected] |
Keywords: myeloma; NSD2; t(4;14); CD38; plasma cell
Received: February 07, 2025 Accepted: March 06, 2025 Published: March 21, 2025
ABSTRACT
Overexpression of the H3K36 histone methyltransferase NSD2 in t(4;14) multiple myeloma (MM) is an early, oncogenic event, and understanding its impact on genomic organisation and expression is relevant to understanding MM biology.
We performed epigenetic, transcriptional and phenotypic profiling of the t(4;14) KMS11 myeloma cell line and its isogenic translocation knock out (TKO) to characterise the sequelae of NSD2 overexpression.
We found a marked global impact of NSD2 on gene expression and DNA organisation implicating cell identity genes; notably the early lymphocyte regulator, LAIR1 and MM cell surface markers, including CD38, a classical marker of plasma cells which was reduced in TKO cells. Plasma cell transcription factors such as PRDM1, IRF4 and XBP1 were unaffected, suggesting a downstream direct gene effect of NSD2 on cell identity. Changes in cell surface markers suggest an altered surface immunophenotype.
Our findings suggest a role for NSD2 in maintaining MM cell identity, with potential implications for future therapeutic strategies based on targeting of NSD2.
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PII: 28706