High expression of Inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia

Inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) is a key regulator for the activity of calcium ion transmembrane transportation, which plays a critical role in cell cycle and proliferation. However, the clinical impact of ITPR2 in cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown. Several microarray datasets were used to evaluate the association between ITPR2 expression and clinical and molecular characteristics. ITPR2 showed a higher expression in CN-AML patients than normal persons. In a cohort of 157 CN-AML patients, high ITPR2 expression (ITPR2high) was associated with dramatically shorter overall survival (OS; P = 0.004) and event-free survival (EFS; P = 0.01), which were also shown in the European Leukemia Net (ELN) intermediate-I genetic category (OS: P = 0.0066; EFS: P = 0.009). Multivariable analyses adjusting for known prognostic factors confirmed ITPR2high to be associated with shorter OS (P = 0.0019) and EFS (P = 0.012). The prognostic value of ITPR2 was further validated in another cohort of 162 CN-AML patients (P = 0.007). In addition, first gene/microRNA expression signatures were derived that associated with ITPR2high on the genome-wide scale, which provided many indications to illustrate the possible mechanisms why ITPR2 could function. These results could aid to identify new targets and design novel therapeutic strategies for CN-AML patients.

• Publication year

  2015

• Venue

  OncoTarget

• Publication date

  2015-01-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/ONCOTARGET.3024PMID 25779662PMCID 4467150
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Brief Report: Genome‐Wide Association Study Identifies ITPR2 as a Susceptibility Gene for Kashin‐Beck Disease in Han Chinese

  2015cited by this paper
• Overexpression of Wilms Tumor 1 Gene as a Negative Prognostic Indicator in Acute Myeloid Leukemia

  2014cited by this paper
• Clinical features of De Novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations

  2014cited by this paper
• Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia

  2014cited by this paper
• MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets

  2014cited by this paper
• High expression of transcription factor 4 (TCF4) is an independent adverse prognostic factor in acute myeloid leukemia that could guide treatment decisions

  2014cited by this paper
• Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence

  2014cited by this paper
• Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway.

  2013cited by this paper
• Cytogenetics of Acute Leukemia

  2013cited by this paper
• Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid.

  2013cited by this paper
• Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients.

  2013cited by this paper
• Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.

  2013cited by this paper
• High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia.

  2012cited by this paper
• miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia.

  2012cited by this paper
• A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.

  2012cited by this paper
• Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia.

  2011influential reference
• MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia

  2011cited by this paper
• DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia.

  2010cited by this paper
• Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study.

  2010influential reference
• BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.

  2010cited by this paper
• ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays.

  2009influential reference
• Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling

  2009cited by this paper
• Review Articles (434 articles)

  2008influential reference
• Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML.

  2008influential reference
• Gene Expression Omnibus ( GEO ) : Microarray data storage , submission , retrieval , and analysis

  2008cited by this paper
• Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia.

  2008cited by this paper
• An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.

  2008influential reference
• From the Cover: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

  2005influential reference
• Cytogenetics in acute leukemia.

  2004cited by this paper
• Articles on similar topics can be found in the following Blood collections Cell Adhesion and Motility (790 articles)

  2004influential reference
• Prognostically useful gene-expression profiles in acute myeloid leukemia.

  2004cited by this paper
• Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm.

  2002cited by this paper
• Apoptosis Induced by Cadmium in Human Lymphoma U937 Cells through Ca2+-calpain and Caspase-Mitochondria- dependent Pathways*

  2000cited by this paper

• ITPR2 Promotes Acute Myeloid Leukemia Progression Through Calcium-Mediated Mitochondrial Dysfunction.

  2026cites this paper
• Discovery metabolomics and genetic analysis reveal lipid pathway alterations associated with malignant phenotype acquisition in pleomorphic adenoma and a novel NTF3::ITPR2 fusion in carcinoma ex pleomorphic adenoma.

  2025cites this paper
• STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells

  2024cites this paper
• ScHGSC-IGDC: Identifying genes with differential correlations of high-grade serous ovarian cancer based on single-cell RNA sequencing analysis

  2024cites this paper
• The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation

  2023influential citation
• The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation

  2023cites this paper
• [Lethal AML? Calcium signalling to the rescue!]

  2023cites this paper
• High trophinin-associated protein expression predicts good survival in acute myeloid leukemia with normal cytogenetics

  2023cites this paper
• Characterization of bone marrow heterogeneity in NK-AML (M4/M5) based on single-cell RNA sequencing

  2023cites this paper
• Put in a “Ca2+ll” to Acute Myeloid Leukemia

  2022cites this paper
• Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential

  2022cites this paper
• Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer

  2022cites this paper
• Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

  2022cites this paper
• Characteristics of genetic alterations of peripheral T‐cell lymphoma in childhood including identification of novel fusion genes: the Japan Children’s Cancer Group (JCCG)

  2021cites this paper
• Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact

  2020cites this paper
• A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes

  2020cites this paper
• Dissecting the Anticancer Mechanism of Trifluoperazine on Pancreatic Ductal Adenocarcinoma

  2019cites this paper
• High NCALD expression predicts poor prognosis of cytogenetic normal acute myeloid leukemia

  2019cites this paper
• Proteomic research in sarcomas – current status and future opportunities

  2019cites this paper
• Integrated multi-omics data analysis identifying novel drug sensitivity-associated molecular targets of hepatocellular carcinoma cells

  2018cites this paper
• Role of Mitochondria-Associated ER Membranes in Calcium Regulation in Cancer-Specific Settings1

  2018cites this paper
• High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia

  2016cites this paper
• High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia

  2016cites this paper
• High expression of MAP7 predicts adverse prognosis in young patients with cytogenetically normal acute myeloid leukemia

  2016cites this paper
• High Expression of CPT 1 A Predicts Adverse Outcomes : A Potential Therapeutic Target for Acute Myeloid Leukemia

  2016influential citation
• The Role of Inositol 1,4,5-Trisphosphate Receptor-Interacting Proteins in Regulating Inositol 1,4,5-Trisphosphate Receptor-Dependent Calcium Signals and Cell Survival

  2016cites this paper
• Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

  2016cites this paper
• The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease.

  2016cites this paper
• A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

  2015cites this paper
• Overexpression of ATP1B1 predicts an adverse prognosis in cytogenetically normal acute myeloid leukemia

  2015cites this paper