Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Myeloid-derived suppressor cells mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies

ABSTRACT: Myeloid-derived suppressor cells mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies

PROVIDER: PRJNA1070688 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27766130.fastq.gz	Fastqsanger.gz
	SRR27766131.fastq.gz	Fastqsanger.gz
	SRR27766132.fastq.gz	Fastqsanger.gz
	SRR27766133.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

Myeloid-derived suppressor cells mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies

Project description:Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlated with poor outcomes in hematologic malignancies. Here, we identify the mitochondrial fitness in MDSCs controlling the efficacy of doxorubicin chemotherapy for lymphoma. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to metabolic reprograming of MDSCs, marked by sustained mitochondrial respiration (OX/PHOS) and higher ATP generation which reduces the AMPK signaling. Furthermore, induced STAT3 signaling in MDSCs enhanced glutamine consumption via the tricarboxylic acid (TCA) cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species (mROS) via regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the antioxidant machinery. We found that targeting the STAT3 pathway or ATP/Itaconate metabolites by blocking β2-AR signaling, the electron transport chain and ATP generation, or itaconate generation, results in disrupted MDSC mitochondrial fitness. This disruption increases the in vivo response to doxorubicin, delaying lymphoma progression.

2024-02-29 | GSE254512 | GEO

Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies.

Project description:Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using β2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.

| S-EPMC10981707 | biostudies-literature

Natural Killer Cell Therapies for Hematologic Malignancies

Project description:Natural Killer Cell Therapies for Hematologic Malignancies

| PRJNA776383 | ENA

Natural Killer Cell Therapies for Hematologic Malignancies

Project description:Natural Killer Cell Therapies for Hematologic Malignancies

| PRJNA776384 | ENA

Germ cell tumor and associated hematologic malignancies

Project description:Germ cell tumor and associated hematologic malignancies

| PRJNA660496 | ENA

Germ cell tumor and associated hematologic malignancies

Project description:Germ cell tumor and associated hematologic malignancies

| PRJNA660497 | ENA

Quassinoid analogs with enhanced efficacy for treatment of hematologic malignancies specifically target the PI3Kgamma isoform

Project description:Development of novel PI3Ks inhibitors is an important strategy to overcome their resistance and poor tolerability in clinical trials. The quassinoid family member Brusatol shows specific inhibitory activity against hematologic malignancies. However, the mechanism of its anti-cancer activity is unknown. We studied the anti-cancer activity of Brusatol on multiple hematologic malignancies derived cell lines by RNA-Seq, mass spectrometry, biochemical pull-down assays, and CRISPR/Cas9 gene knock-out. We demonstrated that the PI3Kgamma isoform was identified as a direct target of Brusatol, and inhibition was lost on PI3Kgamma deficient cells. Novel synthetic analogs were also developed and tested in vitro and in vivo. They shared superior potency in their ability to inhibit malignant hematologic cell lines, and in a xenograft transplant mouse model. They also had minimal toxicity to normal human cells. These new analogs have enhanced potential for development as a new class of PI3K inhibitors for treatment of hematologic malignancies.

2020-03-06 | MSV000085067 | MassIVE

Origins of BRAF-mutant hematologic malignancies and their therapeutic resistance

Project description:Origins of BRAF-mutant hematologic malignancies and their therapeutic resistance

| PRJNA553593 | ENA

Origins of BRAF-mutant hematologic malignancies and their therapeutic resistance

Project description:Origins of BRAF-mutant hematologic malignancies and their therapeutic resistance

| PRJNA553592 | ENA

450K analysis of pediatric histiocytic sarcomas and anteceding hematologic malignancies

Project description:450K analysis of pediatric histiocytic sarcomas and anteceding hematologic malignancies

| PRJNA432268 | ENA