Colony Stimulating Factor 1 Receptor in Acute Myeloid Leukemia

Sletta, Kristine Yttersian; Castells, Oriol; Gjertsen, Bjørn Tore

doi:10.3389/fonc.2021.654817

Cited by 19 publications

(12 citation statements)

References 112 publications

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“…Therefore, the high expression of CXCL10 may be related to the drug resistance mechanism of Crohn's disease. The protein encoded by colony stimulating factor 1 receptor (CSF1R) is the colony stimulating factor 1 receptor, which regulates the proliferation, differentiation and function of macrophages (28). Previous studies con rmed that CSF1R was highly expressed in in ammatory bowel disease, which is consistent with our research results (29,30).…”

Section: Discussionsupporting

confidence: 90%

Uncovering Potential Novel Biomarkers In Crohn's Disease Using Integrated Bioinformatics Analysis

Feng¹

2022

Preprint

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Background: Crohn's disease is a chronic nonspecific intestinal inflammatory disease with unknown etiology. This study aimed to predict potential novel biomarkers of Crohn's disease.Methods: Gene expression datasets of Crohn's disease and normal samples were downloaded from the Gene Expression Omnibus (GEO) database. First, differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) were performed. Common genes (CGs) were obtained by the intersection of differentially expressed genes (DEGs) and optimal modal genes of WGCNA. Subsequently, a protein-protein interaction (PPI) network was established to screen hub genes and then establish a Crohn's disease risk prediction model based on hub genes. A receiver operating characteristic (ROC) curve, and area under the curve (AUC) were used to evaluate the prediction ability of the model. Finally, the mirTarBase database, starBase database, and TargetScan database were used to predict microRNAs (miRNAs) and transcription factors (TFs) that cause Crohn's disease.Results: A total of 74 DEGs were identified. WGCNA showed that the signature gene in the blue module was significantly associated with Crohn's disease (p=4e-6) and obtained 32 CGs. Five hub genes (CDH17, CSF1R, CXCL10, CXCL9, COL3A1) were identified and well predicted Crohn's disease risk (AUC=0.853). Meanwhile, in the miRNA-mRNA regulatory network and TF-mRNA regulatory network, we found that 3 miRNAs (hsa-miR-29a-3p, hsa-miR-29b-3p, hsa-miR-29c-3p) and 2 TFs (TCF4, HINFP) regulate multiple CGs.Conclusions: Five genes (CDH17, CSF1R, CXCL10, CXCL9 and COL3A1), three miRNAs (hsa-miR-29a-3p, hsa-miR-29b-3p, hsa-miR-29c-3p) and two TFs (TCF4, HINFP) may be involved in the pathogenesis of Crohn's disease.

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Section: Discussionsupporting

confidence: 90%

Uncovering Potential Novel Biomarkers In Crohn's Disease Using Integrated Bioinformatics Analysis

Feng¹

2022

Preprint

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“…The binding of M-CSF to its receptor c-Fms results in phosphorylation of c-Fms. Because of the phosphorylation site of the intracellular cytoplasmic tail of c-Fms interacts with growth factor receptor-binding protein-2, a stimulator of the Ras/Raf pathway, ERK is activated for enhancing osteoclast precursors proliferation and survival 36 . Besides, the phosphorylation of ERK also plays a role in maintaining cell polarity during bone resorption 37 .…”

Section: Discussionmentioning

confidence: 99%

Loureirin B downregulates osteoclast differentiation of bone marrow macrophages by targeting the MAPK signaling pathway

Zhang

Liang

Huang

et al. 2022

Sci Rep

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Excessive absorption of osteoclasts will break the balance between osteoclasts and osteoblasts, leading to bone loss, decreased bone density, and increased bone fragility. We have shown that Loureirin B (LrB) can inhibit osteoclasts. In this study, we demonstrated the targeting-inhibitory mechanism of LrB acting on osteoclast precursor. Using SPR, HPLC and MALDI-TOF-MS to capture and analyze the target protein of Loureirin B in bone marrow macrophages (BMMs), we used this method to detect all target proteins that LrB acts on BMMs, and analyzed the distribution and enrichment rate of the target protein by DAVID enrichment analysis. Ledock molecular docking was used to detect the binding of LrB. We used Western Blot for verification. The target proteins of LrB acting on BMMs were Serpine1, Atp6ap1, Dvl1, Rhd, Fzd2, MAPK1, MAP2K2, MAPK3 and so on. MAPK1, MAP2K2 and MAPK3 were the most relevant. LrB treatment attenuated the expression of phosphorylated JNK and p38 kinases of the MAPK signaling pathway. Our research further confirmed that LrB affects the MAPK signaling pathway in BMMs, thereby inhibiting the differentiation of BMMs into osteoclasts. This discovery can confirm the mechanism by which LrB acts on BMMs.

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“…Aiming to modulate the MΦ phenotype in AML is a promising therapeutic approach. Currently, clinical development of CSF1R inhibitors, including PLX3397, for AML treatment is at the early stages [ 90 ]. The efficacy of PLX3397, a FLT3 and CSF1R inhibitor, was demonstrated in relapsed/refractory FLT3-ITD-mutated AML with a safety profile similar to that of other FLT3 inhibitors [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

CSF1R Inhibition Combined with GM-CSF Reprograms Macrophages and Disrupts Protumoral Interplays with AML Cells

Смирнова

Spertini

2021

Cancers

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Relapse is a major issue in acute myeloid leukemia (AML) and while the contribution of gene mutations in developing drug resistance is well established, little is known on the role of macrophages (MΦs) in an AML cell microenvironment. We examined whether myeloblasts could educate MΦs to adopt a protumoral orientation supporting myeloblast survival and resistance to therapy. Flow cytometry analyses demonstrated that M2-like CD163+ MΦs are abundantly present, at diagnosis, in the bone marrow of AML patients. We showed that myeloblasts, or their conditioned medium, polarize monocytes to M2-like CD163+ MΦs, induce the secretion of many protumoral factors, and promote myeloblast survival and proliferation as long as close intercellular contacts are maintained. Importantly, pharmacologic inhibition of the CSF1 receptor (CSF1R), in the presence of GM-CSF, reprogrammed MΦ polarization to an M1-like orientation, induced the secretion of soluble factors with antitumoral activities, reduced protumoral agonists, and promoted the apoptosis of myeloblasts interacting with MΦs. Furthermore, myeloblasts, which became resistant to venetoclax or midostaurin during their interplay with protumoral CD163+ MΦs, regained sensitivity to these targeted therapies following CSF1R inhibition in the presence of GM-CSF. These data reveal a crucial role of CD163+ MΦ interactions with myeloblasts that promote myeloblast survival and identify CSF1R inhibition as a novel target for AML therapy.

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Colony Stimulating Factor 1 Receptor in Acute Myeloid Leukemia

Cited by 19 publications

References 112 publications

Uncovering Potential Novel Biomarkers In Crohn's Disease Using Integrated Bioinformatics Analysis

Uncovering Potential Novel Biomarkers In Crohn's Disease Using Integrated Bioinformatics Analysis

Loureirin B downregulates osteoclast differentiation of bone marrow macrophages by targeting the MAPK signaling pathway

CSF1R Inhibition Combined with GM-CSF Reprograms Macrophages and Disrupts Protumoral Interplays with AML Cells

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