Dysregulation of CCAAT/enhancer binding protein-alpha (CEBPA) expression in the bone marrow of acute myeloid leukemia patients

Abstract

Background Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by accumulation of different types of mutations commonly the CCAAT/enhancer binding protein-alpha (CEBPA). However, the dysregulations of CEBPA expression in AML is still a debatable issue. The aim of the current study was to assess CEBPA gene expression in bone marrow (BM) aspiration specimens of 91 AML patients, compared to 20 control donors of bone marrow transplantation (BMT), using RT-PCR. Data were correlated with patients’ clinico-pathological features, response to treatment, progression-free survival (PFS), and overall survival (OS) rates. Results There was overexpression of CEBPA gene in AML patients compared to normal control [1.7 (0.04–25.6) versus 0.17 (0–4.78), respectively, P < 0.001]. Upregulation of CEBPA expression associated significantly with increased BM hypercellularity, total leucocyte counts, peripheral blood blast cell count, and poor PFS (P < 0.001, 0.002, 0.001, and 0.013, respectively). There was no significant association between CEBPA expression and any other relevant clinico-pathological features or OS rates (P = 0.610) of the patients. ROC analysis for biological relevance of CEBPA expression with AML showed that sensitivity and specificity of CEBPA expression at a cut-off value of 0.28 are 92.3% and 78.6%, respectively (P < 0.001). All patients who had CEBPA overexpression and mutant FLT3 showed BM hypercellularity, adverse cytogenetic risk, increased TLC, and PB blast cells count (P = 0.007, P < 0.001, 0.016, and 0.002, respectively). Conclusion CEBPA overexpression could be used as a genetic biological marker for AML diagnosis, as well as a poor prognostic factor for disease progression. It has no impact on OS rates of the patients.

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

“…Moreover, it had been reported that miR-34a induced cell apoptosis and hindered autophagy by inhibiting the expression of high-mobility group protein 1 (HMG-1) or Histone deacetylase 1 (HDAC1) enzyme [ 40 ]. Additionally, MiR-34a was reported to be a downstream target of the C/EBPα gene which has a critical function in the development and progression of AML [ 41 , 42 ]. Therefore, upregulating miR-34a in AML patients with C/EBPα mutations could be an effective line of treatment [ 42 ].…”

Genetic basis of acute myeloid leukemia (AML): The most common molecular changes in patients with normal karyotype

“…Besides these changes, FLT3-ITD and DNMT3A mutations are the most common in NK AML [2]. Additionally, FLT3 expression is linked to that of CEBPA [3,4]. Due to these findings, NPM1, FLT3, CEBPA, and DNMT3A genes were chosen for this review.…”