Epigenomic profiling of H3K27ac in a primary patient-derived multiple myeloma cell line using two different low-input methods with concordant results

Investigating histone post-translational modifications (PTMs) in cancer, including multiple myeloma (MM), is crucial for elucidating epigenetic mechanisms that drive malignant transformation, disease progression, and drug resistance. Indeed, in MM, aberrant epigenetic mark patterns are increasingly recognized as key contributors to the dysregulation of gene expression programs that promote tumour survival and proliferation. The development of Cleavage Under Targets and Tagmentation (CUT&Tag) has revolutionized genome-wide profiling of histone marks by allowing analysis from low cell numbers and providing notable benefits over traditional ChIP-seq methods. Given this advancement, we utilized this approach in our study by employed two commercially available CUT&Tag workflows to profile five critical histone modifications in two primary multiple myeloma cell lines derived from patients, starting with as few as 50,000 cells. Building on this expertise, the present brief report evaluates and highlight the comparability of these methods through a dedicated H3K27ac experiment demonstrating that both kits yield overlapping genomic profiles with high inter-replicate reproducibility and similar sequencing depth requirements, confirming they are interchangeable and highly effective for low-input epigenomic studies in MM. These methods provide a powerful tool to overcome a major barrier to MM epigenomic research and advance our understanding of its chromatin landscape.