Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia

Huang, Sai; Huang, Zhi; Ma, Chi; Luo, Lan; Li, Yanfen; Wu, Yongli; Ren, Yuan; Feng, Cong

doi:10.21037/atm.2020.02.54

Cited by 11 publications

(15 citation statements)

References 81 publications

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“…Moreover, THP1 cells shows great sensitivity to H3BP treatment (Figure 3) in consistent to that ANP32A is required for mouse bone marrow cell immortalization by MLL-AF9 [12]. Furthermore, one study indicated an overexpression of ANP32A in MLL-translocation subgroups in AML patients than normal BM [13]. Consequently, it would be very interesting that exploration of the promising therapeutic potential of TAT-H3BP combined with other therapeutic agents for relapsed and refractory leukemia and identifying the subtypes of AML sensitive to TAT-H3BP therapeutic strategy accurately in further investigations.…”

Section: Discussionsupporting

confidence: 76%

“…H3BP-GFP competes with ANP32A to bind to H3 and suppresses leukemia cell proliferation ANP32A contributes to unfavorable outcomes for AML patients and is associated with signi cant histone H3 acetylation enrichment and the expression of lipid metabolism genes in leukemogenesis [12,13].…”

Section: Resultsmentioning

confidence: 99%

“…Further understanding of histone acetylation is sure to desire to de ne optimal therapeutic strategies in targeting AML. For instance, recent work revealed ANP32A (acidic nuclear phosphoprotein 32 family member A) as an unfavorable prognostic factor in AML patients and ANP32A promotes leukemogenesis by enhancing histone 3 (H3) acetylation and upregulating the expression of lipid metabolism genes [12][13][14]. These ndings attest ANP32A is an unfavorably prognostic factor of AML and it is of great signi cance to explore whether targeting ANP32A is a novel strategy against AML.…”

Section: Introductionmentioning

confidence: 99%

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Small Peptide Targeting ANP32A as a Novel Strategy For Acute Myeloid Leukemia Therapy

Wang

Guo

Zhang

et al. 2021

Preprint

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Background: Clinic therapy of acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategy. Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for leukemia therapy. Results: To target ANP32A, we identified a peptide that competed with ANP32A to bind to histone 3 (termed as H3-binding peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in leukemia cells. Furthermore, a synthesized membrane-penetrating peptide TAT-H3BP effectively entered into leukemia cells and reproduced such effect. In vivo, TAT-H3BP showed potent efficacy against leukemia: Intra-tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells.Conclusions: Intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML.

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Section: Discussionsupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Small Peptide Targeting ANP32A as a Novel Strategy For Acute Myeloid Leukemia Therapy

Wang

Guo

Zhang

et al. 2021

Preprint

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“…Furthermore, the overexpression of ANP32A was associated with aberrant expression of oncogenes and tumor suppressor, as well as immune-related pathways [ 31 ]. It is possible that individuals carrying genotype T/T of rs8030672 in gene ANP32A may be more susceptible to alterations in the state of gene modifications or DNA damage related to autoimmune regulation [ 20 , 32 , 33 ], when stimulated by certain carcinogen exposures such as acetaldehyde and nicotine.…”

Section: Discussionmentioning

confidence: 99%

Tumor infiltrating lymphocyte signature is associated with single nucleotide polymorphisms and predicts survival in esophageal squamous cell carcinoma patients

Suo

Chen

Bińczyk

et al. 2021

Aging

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Purpose: Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and is associated with a poor prognosis. Stromal tumor infiltrating lymphocytes (sTIL) and certain single nucleotide polymorphisms (SNPs) have been found to be predictive of patient survival. In this study, we explored the association between SNPs and sTIL regarding the predictability of disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and methods: We collected 969 pathologically confirmed ESCC patients from 2010 to 2013 and genotyped 101 SNPs from 59 genes. The number of sTIL for each patient was determined using an automatic algorithm. A Kruskal-Wallis test was used to determine the association between genotype and sTIL. The genotypes and clinical factors related to survival were analyzed using a Kaplan-Meier curve, Cox proportional hazards model, and log-rank test. Results: The median age of the patients was 67 (42-85 years), there was a median follow-up of 851.5 days and 586 patients died. The univariable analysis showed that 10 of the 101 SNPs were associated with sTIL. Six SNPs were also associated with disease-free survival. A multivariable analysis revealed that sTIL, rs1801131, rs25487, and rs8030672 were independent prognostic markers for ESCC patients. The model combining SNPs, clinical characteristics and sTIL outperformed the model with clinical characteristics alone for predicting outcomes in ESCC patients. Conclusion: We discovered 10 SNPs associated with sTIL in ESCC and we built a model of sTIL, SNPs and clinical characteristics with improved prediction of survival in ESCC patients.

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“…MiR-25 was found to be overexpressed in the c-kit subgroup and involved in leukemogenesis in pediatric AML. MiR-106b was significantly upregulated in refractory and relapsed pediatric MLL-rearranged AML (25). MiR-146a and miR-146b were abundant in t(8;21) AML, while miR-155 were abundant in FLT3-ITD AML (26).…”

Section: Genome-wide Microrna Profiles Associated With Clic4 Expressionmentioning

confidence: 96%

Aberrant Chloride Intracellular Channel 4 Expression Is Associated With Adverse Outcome in Cytogenetically Normal Acute Myeloid Leukemia

Huang

Chen

et al. 2020

Front. Oncol.

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Background and Methods: Acute myeloid leukemia (AML), which starts in the bone marrow, is a group of hematopoietic stem cell disorders. Chloride intracellular channel 4 (CLIC4) is regulated by p53, c-Myc, and TGF-β. It induces the NF-κB-dependent activation of HIF (hypoxia-inducible factor) and participates in tumor growth through its microenvironmental function. However, its prognostic value in AML remains unclear, as well as its co-expression biomarkers. In this study, we evaluated the prognostic significance of CLIC4 expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis and multi-omics analysis with weighted correlation network analysis (WGCNA) in the CN-AML group were also presented. Based on CLIC4 and its related genes, microRNA-target gene interaction network analysis and downstream gene ontology analysis were performed to unveil the complex functions behind CLIC4. Results: We demonstrated that the overexpression of CLIC4 was notably associated with unfavorable outcome in the two independent cohorts of CN-AML patients [overall survival (OS) and event-free survival (EFS): P < 0.0001, n = 185; OS: P = 0.016, n = 232], as well as in the European LeukemiaNet (ELN) Intermediate-I group (OS: P = 0.015, EFS: P = 0.012, n = 115), the National Comprehensive Cancer Network Intermediate Risk AML group (OS and EFS: P < 0.0001, n = 225), and the non-M3 AML group (OS and EFS: P < 0.0001, n = 435). Multivariable analysis further validated CLIC4 as a highrisk factor in the CN-AML group. Multi-omics analysis presented the overexpression of CLIC4 as associated with the co-expression of the different gene sets in leukemia, up/downregulation of the immune-related pathways, dysregulation of microRNAs, and hypermethylation around the CpG islands, in open sea regions, and in different gene structural fragments including TSS1500, gene body, 5 UTR region, 3 UTR region, and the first exon. By further performing WGCNA on multi-omics data, certain biomarkers that are co-expressed with CLIC4 were also unveiled.

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Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia

Cited by 11 publications

References 81 publications

Small Peptide Targeting ANP32A as a Novel Strategy For Acute Myeloid Leukemia Therapy

Small Peptide Targeting ANP32A as a Novel Strategy For Acute Myeloid Leukemia Therapy

Tumor infiltrating lymphocyte signature is associated with single nucleotide polymorphisms and predicts survival in esophageal squamous cell carcinoma patients

Aberrant Chloride Intracellular Channel 4 Expression Is Associated With Adverse Outcome in Cytogenetically Normal Acute Myeloid Leukemia

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