&lt;p&gt;Inhibition of CSRP2 Promotes Leukemia Cell Proliferation and Correlates with Relapse in Adults with Acute Myeloid Leukemia&lt;/p&gt;

Wang, Shujuan; Liu, Yajun; Zheng, Ruyue; Wu, Zhenzhen; Fan, Yi; Li, Mengya; Li, Menglin; Li, Tao; Li, Yafei; Jiang, Zhongxing; Wang, Chong; Liu, Yanfang

doi:10.2147/ott.s281802

Cited by 8 publications

(8 citation statements)

References 25 publications

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“…Bone marrow samples from 154 newly diagnosed AML patients (patients with acute promyelocytic leukemia were excluded) and 26 healthy controls were obtained following informed consent at the First Affiliated Hospital of Zhengzhou University between February 2017 and April 2019. Details of treatment regimens were reported ( 17 ). Subjects were followed up until death, loss to follow-up or April 2021.…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were followed up until death, loss to follow-up or April 2021. Complete remission, relapse, risk stratification, overall survival (OS) and relapse-free survival (RFS) were defined as described ( 17 ). The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University and informed consent was obtained according to the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

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Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype

Liu

et al. 2021

Front. Oncol.

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BackgroundThe prognosis of acute myeloid leukemia (AML) with a normal karyotype is highly heterogonous, and the current risk stratification is still insufficient to differentiate patients from high-risk to standard-risk. Changes in some genetic profiles may contribute to the poor prognosis of AML. Although the prognostic value of G protein subunit alpha 15 (GNA15) in AML has been reported based on the GEO (Gene Expression Omnibus) database, the prognostic significance of GNA15 has not been verified in clinical samples. The biological functions of GNA15 in AML development remain open to investigation. This study explored the clinical significance, biological effects and molecular mechanism of GNA15 in AML.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of GNA15 in blasts of bone marrow specimens from 154 newly diagnosed adult AML patients and 26 healthy volunteers. AML cell lines, Kasumi-1 and SKNO-1, were used for lentiviral transfection. Cell Counting Kit-8 (CCK8) and colony formation assays were used to determine cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The relevant signaling pathways were evaluated by Western blot. The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Xenograft tumor mouse model was used for in vivo experiments.ResultsThe expression of GNA15 in adult AML was significantly higher than that in healthy individuals. Subjects with high GNA15 expression showed lower overall survival and relapse-free survival in adult AML with normal karyotype. High GNA15 expression was independently correlated with a worse prognosis in multivariate analysis. Knockdown of GNA15 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. GNA15-knockdown induced down-regulation of p-P38 MAPK and its downstream p-MAPKAPK2 and p-CREB. Rescue assays confirmed that P38 MAPK signaling pathway was involved in the inhibition of proliferation mediated by GNA15 knockdown.ConclusionsIn summary, GNA15 was highly expressed in adult AML, and high GNA15 expression was independently correlated with a worse prognosis in adult AML with normal karyotype. Knockdown of GNA15 inhibited the proliferation of AML regulated by the P38 MAPK signaling pathway. Therefore, GNA15 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype

Liu

et al. 2021

Front. Oncol.

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“…All data were collected independently by two researchers who received training to reliably complete all assessments. Details of treatment regimens are reported [15,16]. Induction chemotherapy regimens include IA and DA regimens: standard-dose cytarabine (Ara-C) 100-200 mg•m −2 •d −1 × 7 d combined with idarubicin 10-12 mg•m −2 •d −1 × 3d or daunorubicin 60 mg•m −2 •d −1 × 3d.…”

Section: Patients and Treatment Regimenmentioning

confidence: 99%

Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia

Hao,

Liu,

Liu

et al. 2024

Clin Exp Med

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Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein–protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

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“…Paschka et al's study of 196 patients with CN-AML also supported the above viewpoint, finding that WT-1 mutation is an independent risk factor for CN-AML [ 16 ]. Recent studies have shown that gene expression levels of CPT1A, TGF β 1, VEGF, CSRP2, and others are all associated with the prognosis of AML [ 17 – 19 ]. As is well known, the prognosis of diseases is influenced by multiple factors, and the relationships between these factors are complex.…”

Section: Introductionmentioning

confidence: 99%

Identification of DUSP7 as an RNA Marker for Prognostic Stratification in Acute Myeloid Leukemia: Evidence from Large Population Cohorts

Gao

2023

Genetics Research

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Background. The problem of prognostic stratification in acute myeloid leukemia (AML) patients still has limitations. Methods. The expression profile data and clinical features of AML patients were obtained from multiple publicly available sources, including GSE71014, TCGA-LAML, and TARGET-AML. Single-cell analysis was performed using the TISCH project. All the analysis was conducted in the R software. Results. In our study, three public AML cohorts, GSE71014, TARGET-AML, and TCGA-AML, were selected. Then, we identified the prognosis-related molecules through bioinformatic analysis. Finally, the DUSP7 was noticed as a risk factor for AML patients, which has not been reported previously. Biological enrichment analysis and immune-related analysis were performed to illustrate the role of DUSP7 in AML. Single-cell analysis indicated that the DUSP7 was widely distributed in various cells, especially in monocyte/macrophages and malignant. Following this, a prognosis model based on DUSP7-derived genes was constructed, which showed a good prognosis prediction ability in all cohorts. Conclusions. Our results preliminarily reveal the role and potential mechanism of DUSP7 in AML, providing direction for future research.

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<p>Inhibition of CSRP2 Promotes Leukemia Cell Proliferation and Correlates with Relapse in Adults with Acute Myeloid Leukemia</p>

Cited by 8 publications

References 25 publications

Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype

Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype

Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia

Identification of DUSP7 as an RNA Marker for Prognostic Stratification in Acute Myeloid Leukemia: Evidence from Large Population Cohorts

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