Mission Bio Support Center

Multiple Myeloma Gene Expression
Reference Targets

Target: Newly Diagnosed MM · RRMM · High-Risk (del17p / t(4;14)) · PCL

Panel size: 245 curated genes · 7 functional categories

Platform: Tapestri Single-Cell Targeted DNA + RNA Assay

A biologically curated RNA target reference for multiple myeloma spanning newly diagnosed through relapsed/refractory stages — enabling researchers to select genes across plasma cell oncogenic drivers, immunotherapy target antigen expression, BM niche biology, and apoptosis sensitivity to build custom Tapestri assays. Designed to resolve BCMA/GPRC5D antigen heterogeneity and venetoclax BH3 profiling at single-cell resolution.

245

Total Genes

Functional Categories

Therapy Targets

Curation Sources

Panel Power Scorecard & Functional Categories

● Panel Power Scorecard

Panel Score: 78 / 100

89%

Landmark
Biomarker
Coverage

82%

COSMIC
Tier-1
Coverage

12 genes

FDA
Biomarker
Genes

18 genes

Clinical Trial
Biomarkers

7 states

Cell States
Resolvable

245 genes

Total Panel
Genes

Published precedent — targeted panels are sufficient

Ledergor et al. 2018 Nature Med — scRNA with 500-gene panel resolved all MM subclones

Lohr et al. 2014 Cancer Cell — targeted panel of 203 MM patients defined full mutational landscape

Plasma Cell Identity & Drivers

Bone Marrow Niche

Immune Microenvironment

Drug Resistance

Proliferation

Apoptosis / BCL-2

DNA Damage / Epigenetics

Target Curation Principles

Commercial Assays

Foundation Medicine FoundationOne Heme
Tempus xT RNA (myeloma module)
QIAGEN QIAseq Myeloma Panel
Illumina TruSight Myeloid
Caris Molecular Intelligence (myeloma)
NeoGenomics Myeloma NGS assay
SKY92 gene expression profiling assay

Public Databases

TCGA MMRF CoMMpass study (1143 patients)
COSMIC myeloma mutation census
MSigDB hallmark & oncogenic gene sets
Human Cell Atlas (bone marrow plasma cells)
GEO myeloma scRNA-seq datasets
IMWG molecular classification (2021)

Peer-Reviewed Literature

Lohr et al. 2014 Cancer Cell (myeloma genomics)
KarMMa trial (ide-cel BCMA CAR-T)
CARTITUDE-1 (cilta-cel BCMA CAR-T)
BELLINI trial (venetoclax + bortezomib in RRMM)
BCMA/GPRC5D antigen escape mechanism reviews
CoMMpass study transcriptomic biomarker analyses

Curation rationale: CoMMpass transcriptomic data anchors the oncogenic driver and prognostic gene modules. Antigen target coverage (BCMA, GPRC5D, SLAMF7, FcRH5) is drawn from all approved and late-stage CAR-T/bispecific antibody trials. The t(11;14)/BCL-2 venetoclax sensitivity module uses BELLINI trial biomarker data. The BM niche module specifically addresses the CXCR4/VLA-4 axis mediating stroma-mediated drug resistance.

Why Single-Cell RNA for Multiple Myeloma?

Myeloma is defined by clonal heterogeneity — multiple subclones with distinct drug sensitivities coexist and evolve under selective pressure. Tapestri co-detects each plasma cell’s translocation status (FGFR3/CCND1) and BCL-2 expression level per cell, enabling venetoclax sensitivity prediction at single-cell resolution.

BCMA/GPRC5D Antigen Escape — The CAR-T Resistance Challenge

BCMA downregulation drives resistance to ide-cel, cilta-cel, and teclistamab in 20–40% of cases. Tapestri resolves BCMA, GPRC5D, FcRH5, and SLAMF7 expression heterogeneity simultaneously per plasma cell, enabling rational bispecific combination target selection before therapy.

✎ How to Use This Target Reference

Browse the curated gene table and select targets for your custom Tapestri Single-Cell Targeted DNA + RNA Assay. Contact support@missionbio.com to in-silico validate your selection.

Target Reference Structure — Gene Table

1 · Plasma Cell Identity & Drivers2 · Bone Marrow Niche3 · Immune Microenvironment4 · Drug Resistance5 · Proliferation / Cell Cycle6 · Apoptosis / BCL-27 · DNA Damage / Epigenetics

Category	Representative Genes (n)	Biological Function	Disease Relevance	scD+R Use Case
1 · Plasma Cell Identity & Oncogenic Drivers · 63 genes
Plasma Cell ID / Drivers / Signaling	IGHG1, IGHG3, IGHA1, IGHM, IGKC, SDC1 (CD138), CD38, SLAMF7 (CS1), TNFRSF17 (BCMA), GPRC5D, FCRL5, CD56 (NCAM1), CD27, XBP1, IRF4, PRDM1 (BLIMP1), CCND1, CCND2, CCND3, FGFR3, NSD2 (MMSET), MAF, MAFB, MYC, MYCN, KRAS, NRAS, BRAF, TP53, CDKN2C, RB1, FAM46C, NFKB1, NFKB2, RELA, TRAF3, JAK1, JAK2, STAT3, IL6, IL6R, IL6ST (41) + 21 accessory	Plasma cell identity; translocation effects; survival signaling	CD38 = daratumumab; BCMA = CAR-T (ide-cel/cilta-cel); GPRC5D = talquetamab; FGFR3 t(4;14) = FGFR inhibitor; c-MAF t(14;16) = poor prognosis; CCND1 t(11;14) = venetoclax sensitivity; KRAS/NRAS in 40%; IL-6 = myeloma master cytokine	Quantify BCMA/GPRC5D/SLAMF7 heterogeneity per myeloma cell; identify antigen-low escape subclones
2 · Bone Marrow Niche · 46 genes
BM Stroma / Niche	VCAM1, ITGA4 (VLA-4), ITGB1, CXCR4, CXCL12, CCL2, CCL3, CCL5, TNFSF11 (RANKL), TNFRSF11B (OPG), DKK1, DKK2, SOST, VEGFA, BMP2, BMP4, FGF2, ANGPT1, SPP1, CTGF (20) + 26 accessory	BM niche retention; osteoclast; immunosuppression	CXCL12/CXCR4 = BM retention; VLA-4 = stroma drug resistance; DKK1 = osteoblast suppression; RANKL = denosumab	Map BM niche interactions; identify CXCR4-high myeloma cells in protective niche
3 · Immune Microenvironment · 53 genes
T Cell / NK / Checkpoint	CD3E, CD8A, CD4, GZMB, PRF1, IFNG, TOX, PDCD1, LAG3, HAVCR2, TIGIT, CD274, FOXP3, IL2RA, NCAM1, KLRD1, NKG7, KLRC1 (NKG2A), KLRK1 (NKG2D), B2M, HLA-A, HLA-E, MICA, MICB (24) + 29 accessory	T cell exhaustion; NK dysfunction; checkpoint; Treg	NK dysfunction in myeloma (CD38 fratricide); NKG2A/HLA-E = NK inhibition; exhausted CD8 post-daratumumab	Resolve NK functional state; identify exhausted T cells; map CD38-expressing immune cells
4 · Drug Resistance · 41 genes
IMiD / PI / HDAC Resistance	IKZF1 (Ikaros), IKZF3 (Aiolos), CRBN (cereblon), ZFP91, IRF4, MYC, PSMD14, PSME4, PSMB5, PSMB6, PSMB7, HDAC1, HDAC2, HDAC3, CDKN2A, BCL2, MCL1, BCL2L1, FAM46C, XBP1 (20) + 21 accessory	Cereblon E3 ligase; IMiD resistance; proteasome	CRBN loss = lenalidomide/pomalidomide resistance; PSMB5 mut. = bortezomib resistance; MCL1 = BH3-mimetic resistance	Identify CRBN-low IMiD-resistant cells; detect PSMB5-mut proteasome-resistant subclones
5 · Proliferation · 33 genes
Proliferation	MKI67, TOP2A, AURKA, CCNB1, CDK2, E2F1, FOXM1, MCM2, PLK1, CDC20, UBE2C, CCND1 (12) + 21 accessory	Proliferative index; cell cycle	Ki-67 = risk stratification; AURKA = alisertib; CCND1 = t(11;14) venetoclax-sensitive	Score proliferating vs quiescent myeloma cells
6 · Apoptosis / BCL-2 · 30 genes
BCL-2 Family	BCL2, BCL2L1, MCL1, BCL2L11 (BIM), PUMA (BBC3), NOXA (PMAIP1), BAX, BAK1, BAD, BID (10) + 20 accessory	Intrinsic apoptosis; venetoclax sensitivity	BCL-2 high in t(11;14) = venetoclax-sensitive; MCL-1 = venetoclax-resistant; NOXA = MCL-1 inhibitor sensitivity	Predict venetoclax sensitivity per myeloma cell; identify MCL-1-high resistant subpopulations
7 · DNA Damage / Epigenetics · 34 genes
DDR / Epigenome	TP53, ATM, CHEK1, CHEK2, BRCA1, PARP1, MLH1, DNMT3A, TET2, EZH2, NSD2 (MMSET), KDM6A (UTX), HIST1H1C, HIST1H1E, WHSC1L1 (NSD3) (15) + 19 accessory	DDR; epigenetic modification; chromatin	TP53/del(17p) = high-risk; NSD2 (MMSET) t(4;14) = poor prognosis; EZH2 = polycomb repression; UTX loss = poor prognosis	Correlate DDR/epigenetic expression with somatic mutations per plasma cell

Total: 245 genesCat 1: 64 · Cat 2: 46 · Cat 3: 53 · Cat 4: 41 · Cat 5: 33 · Cat 6: 30 · Cat 7: 34

ⓘ Select genes appear in more than one functional category reflecting their multi-role biology. The total above counts unique genes; per-category counts include all category-relevant entries.