ArticleJournal of translational medicine2019
Reduced protocadherin17 expression in leukemia stem cells: the clinical and biological effect in acute myeloid leukemia.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The M2 macrophage markerOncoimmunology · 2020Pooled it
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- Genome-wide analysis toward the epigenetic aetiology of myelodysplastic syndrome disease progression and pharmacoepigenomic basis of hypomethylating agents drug treatment response.Human genomics · 2023Article
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- Reduced expression of lncRNA DLEU7-AS1 is a novel favorable prognostic factor in acute myeloid leukemia.Bioscience reports · 2022Article
- Comprehensive analysis of SPAG1 expression as a prognostic and predictive biomarker in acute myeloid leukemia by integrative bioinformatics and clinical validation.BMC medical genomics · 2022Article
- Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.Cancer medicine · 2021Article
- Deciphering molecular heterogeneity in pediatric AML using a cancer vs. normal transcriptomic approach.Pediatric research · 2021Article
- Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia.Clinical epigenetics · 2021Article
- Clinical and prognostic relevance ofPeerJ · 2021Article
- Repression of protocadherin 17 is correlated with elevated angiogenesis and hypoxia markers in female patients with breast cancer.Cancer biomarkers : section A of Disease markers · 2021Article
- Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes.Cell death & disease · 2020Article
- Identification and validation of prognosis-related DLX5 methylation as an epigenetic driver in myeloid neoplasms.Clinical and translational medicine · 2020Article
- PCDH17 functions as a common tumor suppressor gene in acute leukemia and its transcriptional downregulation is mediated primarily by aberrant histone acetylation, not DNA methylation.International journal of hematology · 2020Article
- MiR-23a-3p promoted G1/S cell cycle transition by targeting protocadherin17 in hepatocellular carcinoma.Journal of physiology and biochemistry · 2020Article
- Wnt Signalling in Acute Myeloid Leukaemia.Cells · 2019Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeukemia stem cell (LSC)-enriched genes have been shown to be highly prognostic in acute myeloid leukemia (AML). However, the prognostic value of tumor suppressor genes (TSGs) that are repressed early in LSC remains largely unknown.
methodsWe compared the public available expression/methylation profiling data of LSCs with that of hematopoietic stem cells (HSCs), in order to identify potential tumor suppressor genes in LSC. The prognostic relevance of PCDH17 was analyzed on a cohort of 173 AML patients from The Cancer Genome Atlas (TCGA), and further validated in three independent cohorts (n = 339).
resultsWe identified protocadherin17 (PCDH17) and demonstrated that it was significantly down-regulated and hypermethylated in LSCs compared with HSCs. Our analyses of primary AML patient samples also confirmed these deregulations. Clinically, low PCDH17 expression was associated with female sex (P = 0.01), higher WBC (P < 0.0001), higher percentages of blasts in bone marrow (BM) and peripheral blood (PB) (P = 0.04 and < 0.001, respectively), presence of FLT3-internal tandem duplications (P = 0.002), mutated NPM1 (P = 0.02), and wild-type TP53 (P = 0.005). Moreover, low PCDH17 expression predicted worse overall survival (OS) in four independent cohorts as well as in the molecularly defined subgroups of AML patients. In multivariable analyses, low PCDH17 expression retained independent prognostic value for OS. Biologically, PCDH17 expression-associated gene signatures were characterized by deregulations of EMT- and Wnt pathway-related genes.
conclusionsPCDH17 gene was silenced by DNA methylation in AML. Low PCDH17 expression is associated with distinct clinical and biological features and improves risk stratification in patients with AML.
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