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ABSTRACT Plasma-cell heterogeneity in immunoglobulin light-chain amyloidosis (AL) drives disease variability and clinical outcomes and may be influenced by interactions with the cellular microenvironment, immune cell states, and light-chain (lambda/kappa) subtype. Concurrent multiple myeloma (MM) or precursor conditions (MGUS and sMM) introduce additional layers of cellular complexity. To characterize these processes across disease states, we performed single-cell RNA sequencing on bone marrow samples from 19 patients and identified 13 major cell types across 27 cell clusters, including six transcriptionally distinct plasma-cell subsets. Plasma-cell abundance negatively correlated with CD4+ and CD8+ T-cell levels, indicating reduced T-cell populations associated with high plasma-cell burden. Plasma cells exhibited 138 bidirectional ligand-receptor interactions across 35 significant pairs with 12 immune cell populations mediated through 15 pathways. The ligand/receptor interacting genes CXCR4 and PPIA from granulocyte-monocyte progenitors and monocyte subsets showed significant survival associations, underscoring the prognostic relevance of plasma cell-immune cell communication. T and NK cells exhibited variable exhaustion states, with higher exhaustion in CD4+ T-cells linked to poorer outcomes. Differential expression analysis between kappa and lambda light chain subtypes plasma cells demonstrated increased inflammatory programs in kappa, while lambda plasma cells exhibited stronger unfolded protein response (UPR) and proliferative signatures. Across diagnostic groups, plasma cells formed a continuous transcriptomic spectrum; however, progression from AL-MGUS to AL-SMM to AL-MM was marked by loss of interferon-mediated inflammatory response alongside strong activation of MYC, p53, UPR, and apoptosis pathways, which were most prominent in AL-MM. These findings elucidate key drivers of AL progression, stage/subtype vulnerabilities, revealed microenvironmental interactions, enabling improved patient stratification and targeted therapies. Key points Higher plasma-cell burden is linked to reduced CD4 + /CD8 + T-cell proportions, with distinct exhaustion programs across CD4 + , CD8 + , and NK cells. Selective plasma cell-microenvironment communication networks shape disease biology, with specific ligand-receptor interactions linked to survival risk patterns.