biostudies-literaturePilcher WCU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Multiple Myeloma Research FoundationNCATS NIH HHSNIDDK NIH HHSU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSMultiple Myeloma Research Foundation, Myeloma Solutions FundsMultiple Myeloma Research Foundation Fellowship ProgramPaula C. and Rodger O. Riner Blood Cancer Research FundPaula C. and Rodger O. Riney Blood Cancer Research Fund224-246https://www.ebi.ac.uk/biostudies/studies/S-EPMC12858409biostudies-literatureUnknown7(1)Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing partNature cancerA single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.PMC12858409U24 CA224319R50 CA211466U24CA224319U2CCA233303R50CA211466UL1 TR004419R01CA258776PJ000021702R01 CA2587765K12CA090628P30 CA196521U24CA211006U24 CA211006U2C CA233303K12 CA090628P30CA196521U01DK124165U01 DK124165R35 CA210084Michaud MESlade MDasari SNanda SWyczalkowski MALin RVij RFoltz JAJayasinghe RGRosenblatt JAlaaeldin RSimon VABhasin MDhodapkar MVOhlstrom DKumar SChen ZAvigan DLee BHFehniger TACho HJChen RYao LLagana AHouston AWalker LFiala MAPita-Juarez YSchulman JKim-Schulze SRahman AHGnjatic SDawson TCook AMorgenroth-Rebin JBhasin SSLi YAngeliadis KSatpathy SChiang ILKaragkouni DPabustan NFortier JIbrahim OImmune Atlas ConsortiumMa YLeech JRettig MPDiPersio JFDing LPilcher WCHamilton MSantos JVDFerguson KEKelly GLepisto EVlachos ISRadkevich ERogers JGonzalez-Kozlova EBakhtiari MSong YAcharya CROh STFigueiredo II-Ling CWang JTNie KLonial SThomas BESaldarriaga IFernandez NFD'Souza DStrausbauch MACheloni GMulligan GCao SAnderson EKourelis TSato KKalavros NfalseA single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing part2026-01-01T00:00:00Z2026 Jan2026-06-11T06:03:37.388Z2026-06-11T03:11:58.418ZS-EPMC128584094151405310.1038/s43018-025-01072-4