Collections / Multi-Omic Single-Cell Dissection of Leukemic T-Cell Lymphoma Following CAR T-Cell Therapy [Spatial Transcriptomics]

Multi-Omic Single-Cell Dissection of Leukemic T-Cell Lymphoma Following CAR T-Cell Therapy [Spatial Transcriptomics]

A 63-year-old male who received ciltacabtagene autoleucel (cilta-cel) CAR-T cells and the GPRC5DxCD3 bispecific talquetamab for early relapse of his multiple myeloma (MM) developed a leukemic peripheral T-cell lymphoma (PTCL) with cutaneous and intestinal involvement. Longitudinal single-cell RNA and T-cell receptor sequencing of peripheral blood and bone marrow revealed two hyperexpanded CAR-carrying, exhausted effector-memory T-cell clones with marked immunophenotypic as well as transcriptional alterations and different susceptibilities towards treatment with dexamethasone. Spatial transcriptomes of skin lesions confirmed the aberrant CAR-expressing T cells. Whole genome sequencing revealed three distinct integration sites, within the introns of ZGPAT, KPNA4, and polycomb-associated non-coding RNAs. Pre/post-CAR-T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional sub-clone specific LOH and other secondary mechanisms

Datasets3
Size~74 MB
AssayVisium
Samplehuman · skin of body
KindComparison
www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283145 ↗
Python · lamindb
import lamindb as ln
import spatialdata as sd

coll = ln.Collection.get(key="geo-gse283145")
coll.ordered_artifacts.df()                 # the 3 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]

# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
Visium
Human skin of body
GSM8656736
human skin of body peripheral T-cell lymphoma, not otherwise specified 35 MB 1,921 obs silver H&E
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size35 MB
Obs1,921
silver H&E
Open in Vitessce
Visium
Human skin of body
GSM8656737
human skin of body peripheral T-cell lymphoma, not otherwise specified 9.8 MB 793 obs silver H&E
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size9.8 MB
Obs793
silver H&E Open in Vitessce
Open in Vitessce
Visium
Human skin of body
GSM8656735
human skin of body peripheral T-cell lymphoma, not otherwise specified 30 MB 1,702 obs silver H&E
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size30 MB
Obs1,702
silver H&E Open in Vitessce

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