Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)-gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid-repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF-gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA-box binding protein associated factor 1 and CCCTC-binding factor, which may be potential therapeutic targets of AML.

Expression and prognostic potential of GPX1 in human cancers based on data mining

“…Most AML patients are adults, and the outcome is still worse compared to younger patients. Relapse is common after chemotherapy due to the minimal residual disease in the bone marrow microenvironment (20). In sum, there is still an urgent need to find potential and useful biomarkers to improve diagnosis, treatment, and prognosis in cancer patients.…”

Decitabine combined with RDHAP regimen in relapsed/refractory diffuse large B cell lymphoma

“…Patients were recruited for the study according to the following inclusion criteria: (1) age 14-70 years; (2) histologically confirmed DLBCL; (3) previous cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (RCHOP) or failure of multiline treatments but not chemotherapy with the rituximab plus DHAP (RDHAP) regimen; (4) estimated survival time >3 months; (5) cases deemed unsuitable for transplantation, for reasons including disease progression, age, comorbidities, poor response to previous treatment, previous transplantation failure, and other conditions; (6) no chemotherapy contraindications; (7) at least one measurable lesion; (8) no uncontrolled medical disease. Relapsed DLBCL:complete response (CR) to initial chemotherapy was achieved and relapsed after 6 months.…”

“… 5 , 6 Promising outcomes have been reported with decitabine, a phase‐S DNA methylation inhibitor in hematological and solid tumor malignancies. 7 , 8 , 9 , 10 , 11 Low‐dose decitabine can induce DNA demethylation and hematopoietic stem cell differentiation. Furthermore, decitabine was found to restore chemotherapy sensitivity to anthracyclines by reactivating SMAD1 expression.…”

“…Recently, abnormal DNA methylation was found to be related to the development and chemoresistance of lymphoma 5,6 . Promising outcomes have been reported with decitabine, a phase‐S DNA methylation inhibitor in hematological and solid tumor malignancies 7–11 . Low‐dose decitabine can induce DNA demethylation and hematopoietic stem cell differentiation.…”

“…Furthermore, decitabine was found to restore chemotherapy sensitivity to anthracyclines by reactivating SMAD1 expression 12,13 . Decitabine also has synergistic antitumor effects with cisplatin and cytarabine 8,14 . We conducted a prospective clinical experiment to determine the efficacy and safety of decitabine combined with the RDHAP (rituximab, dexamethasone, cytarabine, and cisplatin) in patients with R/R‐DLBCL.…”