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~78.0 MB
AssayVisium
Samplehuman · skin of body
KindComparison
Flag a data issue
www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283145 ↗
Python · sddb client
from sddb import Catalog

cohort = Catalog().collection("geo-gse283145")
cohort.members        # the 3 datasets as a table

print(cohort.licenses())              # check the terms before you download

sdatas = cohort.to_dict()             # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")
Python · lamindb

Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.

import lamindb as ln

db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse283145")
coll.ordered_artifacts.to_dataframe()   # the 3 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
Shell
# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse283145 --dest data/

Licenses: 3 NCBI GEO policy

Visium
Human skin of body
GSM8656736
human skin of body peripheral T-cell lymphoma, not otherwise specified 36.3 MB 1,921 spots silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size36.3 MB
Spots1,921
silver H&E NCBI GEO policy
Open in Vitessce
Visium
Human skin of body
GSM8656737
human skin of body peripheral T-cell lymphoma, not otherwise specified 10.3 MB 793 spots silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size10.3 MB
Spots793
silver H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human skin of body
GSM8656735
human skin of body peripheral T-cell lymphoma, not otherwise specified 31.4 MB 1,702 spots silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissueskin of body
Conditionperipheral T-cell lymphoma, not otherwise specified
Size31.4 MB
Spots1,702
silver H&E NCBI GEO policy Open in Vitessce

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