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Series GSE218390 Query DataSets for GSE218390
Status Public on Apr 21, 2024
Title RAS Pathway–Mutated Chronic Myelomonocytic Leukemia at the Single Cell Level
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Using single-cell, multi-omics technologies, we sought to dissect the biological mechanisms underlying the initiation and progression of RAS pathway–mutated CMML. We found that RAS pathway mutations induced the transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs), which underwent proliferation and monocytic differentiation in response to cell-intrinsic and -extrinsic inflammatory signaling that also impaired immune cells’ functions. HSPCs expanded at disease progression and relied on the NF-KB pathway effector MCL1 to maintain their survival, which explains why patients with RAS pathway–mutated CMML do not benefit from BCL2 inhibitors such as venetoclax. Our study has implications for developing therapies to improve the survival of patients with RAS pathway–mutated CMML.
 
Overall design Single cell RNA and ATAC sequencing in Lin-CD34+ stem and progenitor cells and mononuclear cells isolated from patients with CMML and RAS pathway mutations at the time of diagnosis or after failure of hypomethylation agent therapy or venetoclax-based therapy
 
Contributor(s) Montalban Bravo G, Ma F, Colla S
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Submission date Nov 20, 2022
Last update date May 02, 2024
Contact name Feiyang Ma
Organization name UCLA
Department Molecular Biology Institute
Lab Pellegrini Lab
Street address 610, Charles Young Dr East, TLSB 3000C
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (47)
GSM6744114 BM Sample 10
GSM6744115 BM Sample 11
GSM6744116 BM Sample 12
Relations
BioProject PRJNA903476

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE218390_ATAC_merged_peak.h5 239.7 Mb (ftp)(http) H5
GSE218390_ATAC_merged_tf.h5 9.2 Mb (ftp)(http) H5
GSE218390_DNA_1-3_4-6_500-xp_250PE_04272022.xlsx 30.8 Kb (ftp)(http) XLSX
GSE218390_Protein_1-6_S4_300-xp_150PE_04282022.xlsx 30.8 Kb (ftp)(http) XLSX
GSE218390_RAW.tar 2.1 Gb (http)(custom) TAR (of H5)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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