Dataset Information

Mutation in the RNA binding protein TIS11D/ZFP36L2 is associated with the pathogenesis of acute leukemia.

ABSTRACT: TIS11D is an AU-rich element binding protein that is involved in RNA metabolism and definitive hematopoiesis. Although disruption of genes related to hematopoiesis often leads to the development of leukemia and lymphoma, the involvement of TIS11D in hematological malignancies remains to be determined. In the present study, we identified a heterozygous frameshift mutation (I373fsX91) in the carboxy-terminus of the TIS11D gene in leukemic cells from a patient with acute myeloid leukemia. Moreover, biallelic inactivation of the TIS11D gene resulting from a hemizygous frameshift mutation (G107fsX80) was identified in the Burkitt's lymphoma cell line DG75. In HeLa cells, overexpression of wild-type TIS11D protein (TIS11D(WT)) induced growth inhibition and an S phase checkpoint response, while the mutant protein (TIS11D(I373fsX91)) showed a diminished effect. Interestingly, this response was accompanied by p21 downregulation, which is frequently seen in the cellular response to ultraviolet irradiation. These data suggest that the dysregulation of TIS11D function is associated with the pathogenesis of certain types of leukemia.

SUBMITTER: Iwanaga E

PROVIDER: S-EPMC7322624 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Mutation in the RNA binding protein TIS11D/ZFP36L2 is associated with the pathogenesis of acute leukemia.

Iwanaga Eisaku E Nanri Tomoko T Mitsuya Hiroaki H Asou Norio N

International journal of oncology 20110101 1

TIS11D is an AU-rich element binding protein that is involved in RNA metabolism and definitive hematopoiesis. Although disruption of genes related to hematopoiesis often leads to the development of leukemia and lymphoma, the involvement of TIS11D in hematological malignancies remains to be determined. In the present study, we identified a heterozygous frameshift mutation (I373fsX91) in the carboxy-terminus of the TIS11D gene in leukemic cells from a patient with acute myeloid leukemia. Moreover, ...[more]

PMID: 21109922

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Project description:Background: The abnormal expression of RNA-binding proteins (RBPs) in various malignant tumors is closely related to the occurrence and development of tumors. However, the role of RBPs in acute myeloid leukemia (AML) is unclear. Methods: We downloaded harmonized RNA-seq count data and clinical data for AML from UCSC Xena, including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohorts. R package edgeR was used for differential expression analysis of 337 whole-blood data and 173 AML data. The prognostic value of these RBPs was systematically investigated by using univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, and multivariate Cox regression analysis. C-index and calibration diagram were used to judge the accuracy of the model, and decision curve analysis (DCA) was used to judge the net benefit. The biological pathways involved were revealed by gene set enrichment analysis (GSEA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the protein-protein interaction (PPI) network performed lateral verification on the selected gene set and LASSO results. Results: A prognostic model of 12-RBP signature was established. In addition, the net benefit and prediction accuracy of the prognostic model and the mixed model based on it were significantly higher than that of cytogenetics. It is verified in the TARGET cohort and shows good prediction effect. Both the selection of our gene set and the LASSO results have high credibility. Most of these pathways are involved in the development of the disease, and they also accumulate in leukemia and RNA-related pathways. Conclusion: The prognosis model of the 12-RBP signature found in this study is an optimized biomarker that can effectively stratify the risk of AML patients. Nomogram based on this prognostic model is a reliable method to predict the median survival time of patients. This study expands our current understanding of the role of RBPs in the occurrence of AML and may lay the foundation for future treatment of the disease.

Dataset Information

Mutation in the RNA binding protein TIS11D/ZFP36L2 is associated with the pathogenesis of acute leukemia.

Publications

Mutation in the RNA binding protein TIS11D/ZFP36L2 is associated with the pathogenesis of acute leukemia.

Similar Datasets

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