Epigenetic and transcriptomic characteristics of t(11;14) MM. (A-C) Uniform manifold approximation and projection (UMAP) showing the distribution of CD138⁺ cells (n = 46 237 cells) collected from 15 patients with MM using the scATAC-seq and scRNA-seq data in the Latent Semantic Indexing method (LSI) space. Each point represents 1 cell. The cells are marked by a color code based on the different clusters (A), fluorescence in situ hybridization, cytogenetic (B), and patient identification (C). (D) Genome accessibility track visualization of CCND1 and MYEOV with peak-to-gene link identified by ArchR for each patient belonging to the t(11;14) (top) and non-t(11;14) (bottom) MM groups. The color of the arcs indicates the correlation strength between the peak and the gene expression (a darker color indicates a stronger correlation). The genes are indicated in red when the gene is on the positive strand (transcription start site [TSS] on the left) and blue when on the negative strand (TSS on the right). The gray boxes highlight the enhancer or promoter regions of the gene of interest. (E) Dot plot representing the scRNA-seq integrated expression of key genes involved in MM biology (CCND1, CCND2, CCND3, FGFR3, and NSD2) and BCL2 family members BCL2, BCL2L1 (BCLXL), BCL2L2 (BCLW), MCL1, BCL2A1, BCL2L11 (BIM), BID, BAX, BAK, BOK, BAD, BMF, BBC3 (PUMA), and PMAIP1 (NOXA) in each MM sample. The t(11;14) MM samples are highlighted in blue, whereas the non-t(11;14) MM samples are highlighted in red. The dot size represents the percentage of cells with values detected in each patient. The color represents the average gene expression in each patient. The dark blue indicates a lower gene expression count, and the light red indicates a higher count. Note that the average expression scales differ for CCND1 vs the other genes. (F) Boxplots comparing the integrated expression of CCND1, BCL2, MCL1, BCL2L1, BBC3, and PMAIP1 in the t(11;14) vs non-t(11;14) MM groups. The false discovery rate (FDR) values associated with each gene are shown at the top of each boxplot comparison. (G) Genome accessibility track visualization of BCL2 with peak-to-gene links for each patient belonging to the t(11;14) (top) and non-t(11;14) (bottom) MM groups. For each group, the peaks panel highlights the different significant peaks identified by ArchR. (H-J) Boxplots indicating the BCL2/BCL2L1 (H), BCL2/MCL1 (I), and MCL1/PMAIP1 gene expression ratios (J) for each MM prevenetoclax sample (left). The boxes highlight the patients with t(11;14) MM. The comparisons between t(11;14) and non-t(11;14) MM groups are shown (right), with t(11;14) in blue and non-t(11:14) in red. The FDR values associated with each gene are shown at the top of each boxplot comparison.