Alternatively spliced CSF3R isoforms in SRSF2 P95H mutated myeloid neoplasms

Wang, Borwyn A.; Mehta, Hrishikesh; Penumutchu, Srinivasa R.; Tolbert, Blanton S.; Kimmel, Marek; Haferlach, Torsten; Maciejewski, Jaroslaw P.; Corey, Seth J.

doi:10.1038/s41375-022-01672-4

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Notably, the key gene PDCD1 serves as an immune checkpoint ( 41 ). Additionally, we identified CSF3R and FCGR1A as myeloid markers ( 42 , 43 ), IL21R and IL4I1 as cytokines and chemokines acting as immune modulators ( 44 , 45 ).These findings suggest that the regulation of cuproptosis can reshape the tumor microenvironment (TME) and consequently impact the efficacy of immunotherapy. Furthermore, we developed a scoring model comprising nine key genes (BCAT1, TLR8, IL4I1, CASP5, FCRL5, CCR8, PDCD1, IFI30, MMP12) associated with cuproptosis and TME.…”

Section: Discussionmentioning

confidence: 79%

Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes

Wang,

Mang,

Guo

et al. 2024

Front. Immunol.

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BackgroundHepatocellular carcinoma (HCC), a prevalent cancer, is linked to cuproptosis in tumor progression. However, cuproptosis's impact on HCC prognosis and its role in the tumor microenvironment remain unclear. We aimed to explore the correlation between cellular cuproptosis and the immune microenvironment in HCC, providing potential immunotherapeutic insights. MethodsExamining cuproptosis-related genes and the immune microenvironment through consensus clustering and WGCNA. Risk models were constructed using LASSO Cox analysis and validated in an independent cohort. Gene expression data from The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database were utilized. We scored cuproptosis expression and explored immunoinfiltration and cell-cell communication. Differential signals in T_memory cells were compared across different cuproptosis levels. ResultsCuproptosis genes associated with fibroblast recruitment (GLS) and macrophage infiltration (FDX1). Liver cancer patients categorized into two subtypes based on cuproptosis gene expression. High expression of DLAT, GLS, and CDKN2A linked to immunosuppression (TGF-β), while high FDX1, MTF1, LIAS, and LIPT1 expression enhanced communication with non-immune cells. Developed reliable prognostic signature score and nomogram using cuproptosis-related genes. Single-cell analysis revealed differences in T_memory and TAM infiltration based on cuproptosis scores, with SPP1 and MIF as dominant signaling molecules. Finally, the results of in vitro experiments showed that when DLAT or CDKN2A was knocked down, the proliferation, migration, and invasion of HCC cells were significantly decreased. ConclusionOur study demonstrates that cuproptosis affects the immune microenvironment and cell-cell communication. Identified 9 genetic markers predicting survival outcomes and immunotherapy responses. Evaluating cuproptosis signaling can optimize immunotherapeutic strategies for hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 79%

Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes

Wang,

Mang,

Guo

et al. 2024

Front. Immunol.

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CSF3R mutated myeloid neoplasms: Beyond chronic neutrophilic leukemia

Mohamed,

Gao,

Chen

et al. 2024

Human Pathology

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Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies

Zhang,

Zhu,

Peng

et al. 2024

Cancer Cell Int

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The serine/arginine-rich splicing factors (SRSFs) play an important role in regulating the alternative splicing of precursor RNA (pre-RNA). During this procedure, introns are removed from the pre-RNA, while the exons are accurately joined together to produce mature mRNA. In addition, SRSFs also involved in DNA replication and transcription, mRNA stability and nuclear export, and protein translation. It is reported that SRSFs participate in hematopoiesis, development, and other important biological process. They are also associated with the development of several diseases, particularly cancers. While the basic physiological functions and the important roles of SRSFs in solid cancer have been extensively reviewed, a comprehensive summary of their significant functions in normal hematopoiesis and hematopoietic malignancies is currently absent. Hence, this review presents a summary of their roles in normal hematopoiesis and hematopoietic malignancies. Graphical Abstract

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Alternatively spliced CSF3R isoforms in SRSF2 P95H mutated myeloid neoplasms

Cited by 3 publications

References 46 publications

Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes

Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes

CSF3R mutated myeloid neoplasms: Beyond chronic neutrophilic leukemia

Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies

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