ABSTRACT
BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most commonly diagnosed childhood malignancy worldwide and is especially common in Mexico. Additionally, the number of cases has increased in recent years. Thus, it is very important to develop molecular strategies to diagnose leukemia. The aim of this study was to investigate MYB expression and to determine its impact on the diagnosis of B-ALL. METHODS: We analyzed the B-ALL gene expression profile by microarray data mining. Bioinformatics analysis was performed to identify the genes that are overexpressed in leukemia. We determined that MYB was highly expressed in leukemia. Then, we validated MYB expression in 70 patients with B-ALL and in 16 healthy controls (HCs) using qRT-PCR. The results were statistically analyzed using the Kolmogorov-Smirnov Z test, Mann-Whitney U test, receiver operating characteristic curves, and the Youden index. RESULTS: The microarrays showed that MYB was overexpressed in B-ALL patients with a fold change of 57.8728 and a P value of 2.56-195 . MYB expression showed great variability among the patients analyzed. However, compared to the HCs, the B-ALL patients had a P value < .0001, an area under the curve of 0.813, and a Youden index of 1.46, indicating the statistical significance. CONCLUSION: MYB expression in B-ALL cells could be a potential molecular marker for childhood leukemia.
Subject(s)
B-Lymphocytes , Genes, myb , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Child , Child, Preschool , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Pathology, MolecularABSTRACT
B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.
