Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

Sarojam, Santhi; Raveendran, Sureshkumar; Vijay, Sangeetha; Sreedharan, Jayadevan; Narayanan, Geetha; Subramanian, Hariharan

doi:10.7314/apjcp.2015.16.9.3785

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…Metzeler et al report were the only study in line with our findings (Metzeler et al, 2011). Regarding our analyses, the TET2mut did not show any correlation with FLT3, NPM1 and CEBPA expression levels (Ishfaq et al, 2012;Sarojam et al, 2015;Alarbeed et al, 2021). Since the previous studies evaluated the molecular prognostic markers through the sequencing method, this discrepancy might be caused by the difference in method.…”

Section: Discussionsupporting

confidence: 75%

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients

Chehreghani

Sadeghian

Ayatollahi

et al. 2022

Asian Pac J Cancer Prev

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Acute myeloid leukemia (AML) is a heterogeneous clonal disease that is considered to originate from hematopoietic stem cells, which are characterized by impaired myelopoiesis and blast proliferation. TET oncogene family member 2 (TET2) mutations are frequent in myeloid malignancies and several studies have assessed the clinical importance of TET2 mutations. However, its frequency ratio has not yet been fully clarified. Method: Hence, our study was aimed to analyze TET2mut in patients with de-novo AML and their association with clinical, molecular characteristics and Nucleophosmin 1 (NPM1), Fms-like tyrosine kinase 3 (FLT3), CCAAT Enhancer Binding Protein Alpha (CEBPA) and Wilms’ tumor protein ( WT1 ) gene expression. Fifty-one Iranian patients were screened by polymerase chain reaction (PCR) and direct sequencing to evaluate TET2 mutations frequency. Results: Out of all patients, 10 mutations in 8 patients (15.6%) were detected and closely associated with higher age and higher hemoglobin levels (p-value <0.05). Although FLT3, NPM1 and CEBPA gene expression did not show any significant correlation with TET2mut, cytogenetically normal acute myeloid leukemia (CN-AML) patients appear to bear TET2mut more frequently with lower platelet counts. Monocyte-lineages leukemia has seemed to be more linked with TET2mut in these patients. Conclusion: Our study suggests the frequency of TET2mut in our study (15.6%) is in line with previous studies and reveals the critical role of TET2 in myeloid transformation, especially in leukemia with monocytic subtypes.

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Section: Discussionsupporting

confidence: 75%

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients

Chehreghani

Sadeghian

Ayatollahi

et al. 2022

Asian Pac J Cancer Prev

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“…Intriguingly, without any microscopically detectable chromosome abnormalities in its leukemic blast, CN-AML harbour aberrantly expressed genes and microRNAs, mutations, epigenetic changes that can be used as potential prognostic markers (8). It is now recognized that WT1, ASXL1, DNMT3A, FLT3-ITD and TET2 mutations presence in CN-AML represent a subgroup of patients with unfavorable prognosis, while NPM1 and CEBPA are associated with favorable prognosis (9)(10)(11)(12)(13)(14)(15). Furthermore, unfavorable prognostic factors include high expression of CPT1A, ATP1B1, RUNX1, MAPKBP1, MAP7, ERG, DNMT3B, miR-3151, miR-155, etc.…”

Section: Introductionmentioning

confidence: 99%

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

Huang¹,

Huang²,

Ma³

et al. 2020

Ann Transl Med

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Background: Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) is a novel regulator of histone H3 acetylation and promotes leukemogenesis in acute myeloid leukemia (AML). However, its prognostic value in AML remains unclear.Methods: In this study, we evaluated the prognostic significance of ANP32A expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis in CN-AML group was also presented. Based on the ANP32A expression, its related genes, dysregulation of pathways, interaction network analysis between microRNAs and target genes, as well as methylation analysis were performed to unveil the complex functions behind ANP32A.

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“…As mentioned above, CEBPA sm AMLs frequently harbor mutations in genes, such as NPM1, FLT3, or ASXL1. 78,79 Thus, these mutant genes seem to collaborate with single mutations in CEBPA (mostly N-terminal) to drive AML. An additional line of evidence to this statement is observed in families with germline N-terminal CEBPA sm .…”

Section: Mutant C/ebpa As a Driver Of Amlmentioning

confidence: 99%

Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation

Avellino

Delwel

2017

Blood

136

110

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One of the most studied transcription factors in hematopoiesis is the leucine zipper CCAAT-enhancer binding protein α (C/EBPα), which is mainly involved in cell fate decisions for myeloid differentiation. Its involvement in acute myeloid leukemia (AML) is diverse, with patients frequently exhibiting mutations, deregulation of gene expression, or alterations in the function of C/EBPα. In this review, we emphasize the importance of C/EBPα for neutrophil maturation, its role in myeloid priming of hematopoietic stem and progenitor cells, and its indispensable requirement for AML development. We discuss that mutations in the open reading frame of CEBPA lead to an altered C/EBPα function, affecting the expression of downstream genes and consequently deregulating myelopoiesis. The emerging transcriptional mechanisms of CEBPA are discussed based on recent studies. Novel insights on how these mechanisms may be deregulated by oncoproteins or mutations/variants in CEBPA enhancers are suggested in principal to reveal novel mechanisms of how CEBPA is deregulated at the transcriptional level.

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Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

Cited by 10 publications

References 34 publications

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients

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

Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation

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