CCAAT/enhancer binding protein α gene expression in Egyptian patients with acute myeloid leukemia

Kassem, Neemat; Fahmy, Abd El-Gawad; Desoky, Mohamed A. El; Medhat, Nashwa; Zawam, Hamdy

doi:10.1016/j.jnci.2013.02.002

Cited by 7 publications

(13 citation statements)

References 18 publications

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“…In contrast, Kassem et al. () observed decreased levels of CEBPA expression in AML patients (high expression in 27.5% of cases versus low expression in 72.5% of cases) with 63% of high‐level CEBPA expression cases belonging to the M3 subtype (Van Doorn et al., ; Kassem et al., ). The latter study strongly opposes our predictions, which are based on extensive literature wherein the role of these molecules in normal myeloid progenitor differentiation has been described as that of a tumor suppressor/differentiative agent (Krug et al., ; Silva et al., ; Tada et al., ).…”

Section: Discussionmentioning

confidence: 96%

“…Disruption of CEBPA expression has been reported in the presence of several translocations involving RUNX1 such as t(8;21) RUNX1‐ETO, t(12;21) RUNX1‐TEL, and t(3;21) RUNX1‐EVI1. These translocations specially lead to suppression of CEBPA mRNA expression or CEBPA translation (Grossmann et al., ; Kassem et al., ). Similarly, RUNX1 gene deletions also lead to a reduction in CEBPA expression.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia

Salarpour

Goudarzipour

Mohammadi

et al. 2017

Annals of Human Genetics

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The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR. Our results reveal that CEBPA and RUNX1 gene expression levels were unexpectedly and significantly higher in patients with AML when compared to the levels detected in the normal control group (P < 0.0001). Furthermore, the correlation between CEBPA and RUNX1 was significant and positive (P-value: 0.011, r: 0.257). Our data contradicts the widely established role of CEBPA and RUNX1 in myeloid differentiation, as we saw lower levels of CEBPA and RUNX1 expression to be exhibited in patients with AML. Likely, our data demonstrates that higher levels of CEBPA and RUNX1 expression were closely correlated with reduced myeloid maturation, but this idea needs to approved. It suggests that despite the current established functions of genes involved in cell differentiation, the leukemogenesis process has the capability to transform normal hematopoietic precursors in a manner that may employ the differentiation related gene at the service of malignancy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia

Salarpour

Goudarzipour

Mohammadi

et al. 2017

Annals of Human Genetics

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“…Clinical and genetic prognostic markers are important in the classifi cation of leukemia patients. Aberrant chromosomal translocations and gene mutations frequently occur in the transcriptional factor that lead to uncontrolled proliferation of lymphoid and myeloid progenitors (1)(2)(3)(4). The CEBPA gene is a member of the leucine zipper family of the transcription factor family that is essential for the differentiation of myeloid cells (5).…”

Section: Introductionmentioning

confidence: 99%

“…The CEBPA gene located on chromosome 19 q13.1 encodes the basic leucin zipper (bZIP) family of the transcription factors (6). It is expressed at high levels during myeloid cell differentiation and binds to the promoters of multiple specifi c genes at different levels of myeloid linage maturation (2). In AML patients, it was reported that two types of mutations in CEBPA gene exist; N terminal and C terminal (2,5,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…It is expressed at high levels during myeloid cell differentiation and binds to the promoters of multiple specifi c genes at different levels of myeloid linage maturation (2). In AML patients, it was reported that two types of mutations in CEBPA gene exist; N terminal and C terminal (2,5,(7)(8)(9)(10)(11). The N terminal mutations are located between the major translational start site and the second ATG further downstream lead to premature stop of translation of the wild type p 42 CEBPA protein, while preserving translation of a short p30 isoform that suppresses the function of the full length protein.…”

Section: Introductionmentioning

confidence: 99%

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Determination of CEBPA mutations by next generation sequencing in pediatric acute leukemia

Akın¹,

Öner²,

Kürekçi³

et al. 2018

BLL

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Association between the CEBPA and c-MYC genes expression levels and acute myeloid leukemia pathogenesis and development

et al. 2020

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CEBPA and c-MYC genes belong to TF and play an essential role in hematologic malignancies development. Furthermore, these genes also co-regulate with RUNX1 and lead to bone marrow differentiation and may contribute to the leukemic transformation. Understanding the function and full characteristics of selected genes in the group of patients with AML can be helpful in assessing prognosis, and their usefulness as prognostic factors can be revealed. The aim of the study was to evaluate CEBPA and c-MYC mRNA expression level and to seek their association with demographical and clinical features of AML patients such as: age, gender, FAB classification, mortality or leukemia cell karyotype. Obtained results were also correlated with the expression level of the RUNX gene family. To assess of relative gene expression level the qPCR method was used. The expression levels of CEBPA and c-MYC gene varied among patients. Neither CEBPA nor c-MYC expression levels differed significantly between women and men (p=0.8325 and p=0.1698, respectively). No statistically significant correlation between age at the time of diagnosis and expression of CEBPA (p=0.4314) or c-MYC (p=0.9524) was stated. There were no significant associations between relative CEBPA (p=0.4247) or c-MYC (p=0.4655) expression level and FAB subtype and mortality among the enrolled patients (p=0.5858 and p=0.8437, respectively). However, it was observed that c-MYC and RUNX1 expression levels were significantly positively correlated (rS=0.328, p=0.0411). Overall, AML pathogenesis involves a complex interaction among CEBPA, c-MYC and RUNX family genes.

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CCAAT/enhancer binding protein α gene expression in Egyptian patients with acute myeloid leukemia

Abstract: We conclude that the majority of the AML patients analyzed, express low levels of C/EBPa mRNA. However, a subset of patients represented by the M3 subtype, express higher levels of C/EBPa.

Cited by 7 publications

References 18 publications

Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia

Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia

Determination of CEBPA mutations by next generation sequencing in pediatric acute leukemia

Association between the CEBPA and c-MYC genes expression levels and acute myeloid leukemia pathogenesis and development

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