Aberrantly expressed transcription factors C/EBP and SOX4 have positive effects in the development of chronic myeloid leukemia

Abstract

The aim of the present study was to examine the expression and significance of CCAAT/enhancer binding protein α (C/EBPα) and SRY‑related high mobility group box containing transcription factor 4 (SOX4) in chronic myeloid leukemia (CML). Bone marrow samples were collected from patients with CML, and peripheral blood mononuclear cells were collected from healthy controls. Protein and mRNA were extracted from the collected samples, and analyzed using western blotting and reverse transcription‑quantitative polymerase chain reaction analyses, respectively. Spearman's method was used to evaluate the correlation between the expression levels of these two genes, with P<0.05 considered to indicate a statistically significant difference. A total of 79 patients, including 57 patients with newly diagnosed CML and 22 patients treated with imatinib therapy, and 30 controls were enrolled. The expression of SOX4 was upregulated in the patients with CML, whereas the expression of C/EBPα was downregulated (P<0.05). However, no differences were observed among the chronic, accelerated and blastic CML phases, respectively (P>0.05). In addition, no associations were found between the changes in expression and age, gender, white blood cells or the expression of breakpoint cluster region/abelson in patients (P>0.05). However, the expression of SOX4 was negatively correlated with the expression of C/EBPα (P<0.01). Following imatinib treatment, the expression of SOX4 was downregulated in the progression‑free patients, but upregulated in the blastic phase patients, whereas the expression of C/EBPα showed the opposite trend. Therefore, C/EBPα and SOX4 were important and negatively associated with the process of CML, and the C/EBPα‑SOX4 axis may be a novel potential therapeutic target for the treatment of CML.

Vitamin E in Chronic Myeloid Leukemia (CML) Prevention

“…The progression of CML to blast crisis is correlated with down-modulation of C/EBP-alpha contributing to the differentiation block, enhanced proliferation, and development of acute myelogenous leukemia [16,17]. The level of C/EBPα expression is significantly declined in CML patients [18]. Currently, the deregulation of C/EBP alpha is considered as a paradigm of leukemogenesis [19].…”

Behind the scenes with basophils: an emerging therapeutic target

“…reduced expression and activity) has been found in AML patients and as such, been suggested as an important contributor to the pathogenesis of AML: C/EBPα may contribute to the blockage in differentiation along hematopoietic lineages that is characteristic of AML [ 47 , 48 ]. Lower expression of C/EBPα has also been observed in patients with CML (bone marrow samples) as compared to controls (peripheral blood samples) [ 49 ]. Loss of function of Ikaros has been detected in AML that progressed from prior MPNs and in the blast crisis and accelerated phases of CML [ 50 , 51 ].…”