<scp><i>FAM213A</i></scp> is linked to prognostic significance in acute myeloid leukemia through regulation of oxidative stress and myelopoiesis

Oh, Chang‐Kyu; Ha, Mihyang; Han, Myoung‐Eun; Heo, Hye Jin; Myung, Kyungjae; Lee, Yoonsung; Oh, Sae‐Ock; Kim, Yun Hak

doi:10.1002/hon.2728

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Transcriptomic variables have higher predictive accuracy than clinical or genetic variables in myelodysplastic syndrome (13), and similar trends were recently observed in AML (14). However, the current widely used risk-stratification system (European Leukemia Net (ELN)2017 risk category) recommended by the National Comprehensive Cancer Network (NCCN) AML guideline (15) was constructed based on genetic variables, without considering transcriptomic changes (14). Recently, increasing numbers of prognostic models for AML based on transcriptomic data were reported, encompassing distinct biological processes such as immunity (16)(17)(18), autophagy (19), etc.…”

Section: Introductionsupporting

confidence: 77%

A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes

et al. 2022

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Accurate prognostic stratification of patients can provide guidance for personalized therapy. Many prognostic models for acute myeloid leukemia (AML) have been reported, but most have considerable inaccuracies due to contained variables with insufficient capacity of predicting survival and lack of adequate verification. Here, 235 genes strongly related to survival in AML were systematically identified through univariate Cox regression analysis of eight independent AML datasets. Pathway enrichment analysis of these 235 genes revealed that the IL-2/STAT5 signaling pathway was the most highly enriched. Through Cox proportional-hazards regression model and stepwise algorithm, we constructed a six-gene STAT5-associated signature based on the most robustly survival-related genes related to the IL-2/STAT5 signaling pathway. Good prognostic performance was observed in the training cohort (GSE37642-GPL96), and the signature was validated in seven other validation cohorts. As an independent prognostic factor, the STAT5-associated signature was positively correlated with patient age and ELN2017 risk levels. An integrated score based on these three prognostic factors had higher prognostic accuracy than the ELN2017 risk category. Characterization of immune cell infiltration indicated that impaired B-cell adaptive immunity, immunosuppressive effects, serious infection, and weakened anti-inflammatory function tended to accompany high-risk patients. Analysis of in-house clinical samples revealed that the STAT5-assocaited signature risk scores of AML patients were significantly higher than those of healthy people. Five chemotherapeutic drugs that were effective in these high-risk patients were screened in silico. Among the five drugs, MS.275, a known HDAC inhibitor, selectively suppressed the proliferation of cancer cells with high STAT5 phosphorylation levels in vitro. Taken together, the data indicate that the STAT5-associated signature is a reliable prognostic model that can be used to optimize prognostic stratification and guide personalized AML treatments.

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Section: Introductionsupporting

confidence: 77%

A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes

et al. 2022

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“…In previous studies, we used zebrafish embryos to investigate the function of target genes with morpholino injection for the knockdown 3,13 . In the present study, splicing‐blocking morpholino was injected into zebrafish embryos to reduce the expression of tpd52 .…”

Section: Resultsmentioning

confidence: 99%

“…As there is the production of undifferentiated myeloid cells, the bone marrow cannot produce normal red blood cells or white blood cells important for homoeostasis within the circulation system. The reduced production of normal blood cells causes fever, fatigue, dizziness, weight loss or bruising 2–4 . The prognosis of AML can be categorised by cytogenetic factors.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, zebrafish embryos are transparent when verifying the expression of target genes during development using in situ hybridisation or immunohistochemistry. For those reasons, zebrafish embryos were used as in vivo models in many studies to investigate the function of leukaemia‐related genes, which suggested that leukaemia‐related genes are linked to the haematological process in zebrafish embryos 3,13,15 …”

Section: Introductionmentioning

confidence: 99%

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AML poor prognosis factor, TPD52, is associated with the maintenance of haematopoietic stem cells through regulation of cell proliferation

Kang

Kim

Lee

et al. 2020

J of Cellular Biochemistry

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Acute myeloid leukaemia (AML) is a blood cancer where undifferentiated myeloid cells are increased in the bone marrow and peripheral blood. As AML is dangerous and shows poor prognosis, many researchers categorised the relevant cytogenetic factors according to risk and prognosis. However, the specific reasons for poor cytogenetic factors remain unknown. We analysed a large data set from AML patients and found that TPD52 expression is elevated in patient groups with poor cytogenetic factors. As the amino acid sequence of TPD52 is evolutionally conserved in vertebrates, zebrafish embryos were used to investigate the function of TPD52. Since myeloid‐biased haematopoietic stem cells (HSCs) are relevant to AML, the function of TPD52 in the development of HSCs was investigated. We determined that the zebrafish paralog, tpd52, is important for the maintenance of HSCs through regulation of cell proliferation. As tpd52 is linked to cell proliferation in zebrafish embryos, the proliferation‐related gene, CD59, was correlated to TPD52 in every AML cohort with a high correlation coefficient. We suggest that TPD52 can be a novel therapeutic target for AML patients with poor cytogenetic factors. Additionally, more studies between TPD52 and CD59 will further increase the value of TPD52 as a novel target.

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“…WISH was performed in 2 days post-fertilization (dpf) embryos. The overall process for WISH was conducted according to previous studies ( Oh et al, 2020 ; Kang et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments

Sung

Lee

et al. 2021

Front. Genet.

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Glioma is the most common primary malignant tumor that occurs in the central nervous system. Gliomas are subdivided according to a combination of microscopic morphological, molecular, and genetic factors. Glioblastoma (GBM) is the most aggressive malignant tumor; however, efficient therapies or specific target molecules for GBM have not been developed. We accessed RNA-seq and clinical data from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, and the GSE16011 dataset, and identified differentially expressed genes (DEGs) that were common to both GBM and lower-grade glioma (LGG) in three independent cohorts. The biological functions of common DEGs were examined using NetworkAnalyst. To evaluate the prognostic performance of common DEGs, we performed Kaplan-Meier and Cox regression analyses. We investigated the function of SOCS3 in the central nervous system using three GBM cell lines as well as zebrafish embryos. There were 168 upregulated genes and 50 downregulated genes that were commom to both GBM and LGG. Through survival analyses, we found that SOCS3 was the only prognostic gene in all cohorts. Inhibition of SOCS3 using siRNA decreased the proliferation of GBM cell lines. We also found that the zebrafish ortholog, socs3b, was associated with brain development through the regulation of cell proliferation in neuronal tissue. While additional mechanistic studies are necessary, our results suggest that SOCS3 is an important biomarker for glioma and that SOCS3 is related to the proliferation of neuronal tissue.

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FAM213A is linked to prognostic significance in acute myeloid leukemia through regulation of oxidative stress and myelopoiesis

Cited by 11 publications

References 30 publications

A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes

A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes

AML poor prognosis factor, TPD52, is associated with the maintenance of haematopoietic stem cells through regulation of cell proliferation

SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments

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