Transcript-Level Dysregulation of Family Genes in Acute Myeloblastic Leukemia.

The expression of apoptosis-related family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in , , and was statistically significant. In a group of patients resistant to chemotherapy, overexpression of was manifested. In agreement with the literature data, our results reveal that is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some family members, in particular and , were associated with poor outcome.