 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 17, 2024 |
| Title |
Single cell multi-omics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The advent of tyrosine kinase inhibitors (TKIs) as treatment of Chronic Myeloid Leukemia (CML) is a paradigm in molecularly targeted cancer therapy. Nonetheless, TKI insensitive leukemia stem cells (LSCs) persist in most patients, even after years of treatment. Here, we used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to generate high-resolution single cell multiomics maps from CML patients stratified according to molecular response (BCR-ABL IS %) following 12 months of TKI therapy. Simultaneous measurement of global gene expression profiles together with >40 surface markers from the same cells revealed that each patient harbored a unique composition of stem and progenitor cells at diagnosis demonstrating that cellular heterogeneity is a hallmark of CML. The patients with treatment failure at 12 months of therapy had markedly higher abundance of molecularly defined primitive cells at diagnosis compared to the optimal responders. The multi-modal feature landscape enabled visualization of the primitive fraction as a mix of Lin-CD34+38-/low BCR-ABL1+ LSCs and BCR-ABL1- HSCs in variable ratio across patients and guided their prospective isolation by a combination of CD26 and CD35 cell surface markers.
|
| |
|
| Overall design |
We performed CITE-seq on two FACS sorted cell populations (Lin-CD34+, Lin-CD34+CD38-) from nine CML bone marrow samples from patients with chronic phase CML at diagnosis.
NOTE FROM SUBMITTER: The data comes from living human subjects which is why we cannot provide the raw sequences. This is to be complaint with the GDPR that operates in the EU from which this data comes.
|
| |
|
| Contributor(s) |
Warfvinge R, Soneji S, Karlsson G |
| Citation(s) |
37919606 |
| |
| Submission date |
Jun 30, 2023 |
| Last update date |
Jan 18, 2024 |
| Contact name |
Shamit Soneji |
| Organization name |
BMC
|
| Street address |
Solvegatan 19
|
| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (17)
|
| GSM7520162 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML1_34p] |
| GSM7520163 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML2_34p2] |
| GSM7520164 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML2_38n2] |
| GSM7520165 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML3_34p] |
| GSM7520166 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML3_38n] |
| GSM7520167 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML4_34p] |
| GSM7520168 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML4_38n] |
| GSM7520169 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML5_34p] |
| GSM7520170 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML5_38n] |
| GSM7520171 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML6_34p] |
| GSM7520172 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML6_38n] |
| GSM7520173 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML7_34p] |
| GSM7520174 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML7_38n] |
| GSM7520175 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML8_34p] |
| GSM7520176 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML8_38n] |
| GSM7520177 |
CML Chronic Phase, Diagnosis, Lin-CD34+, CITEseq [CML9_34p] |
| GSM7520178 |
CML Chronic Phase, Diagnosis, Lin-CD34+CD38-, CITEseq [CML9_38n] |
|
| Relations |
| BioProject |
PRJNA989536 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236233_RAW.tar |
274.8 Mb |
(http)(custom) |
TAR (of TAR) |
| Processed data provided as supplementary file |
| Raw data not provided for this record |
|
|
|
|
 |
Less...
More...