MECOM and BAALC gene expression profiles in Egyptian patients with acute myeloid leukemia by next generation sequencing

Abstract

Background Acute myeloid leukemia (AML) is a challenging heterogenous hematologic malignancy characterized by suboptimal outcomes. Genetic characterization of AML enhanced the understanding of individualized patient’s risk and led to the development of new therapeutic strategies. Gene expression analysis facilitates detection of new diagnostic, prognostic, and predictive biomarkers. This necessitates the expansion of diagnostic testing with higher throughput technologies, such as targeted next-generation sequencing (NGS).Objectives To study the expression profiles of MECOM and BAALC genes in a cohort of newly diagnosed Egyptian AML patients via Oncomine Myeloid Research assay (OMA) by NGS technology in addition to studying their potential prognostic role and impact on overall survival (OS).Methods The OMA was used to evaluate the expression levels of MECOM and BAALC genes and five control genes (FBXW2, PUM1, TRIM27, PSMB2, and EIF2B1), in twenty-four newly diagnosed AML patients by NGS technology, using RNA extracted from bone marrow aspirate (BMA) specimens.Results Gene expression analysis of MECOM and BAALC genes revealed that MECOM overexpression was significantly associated with the presence of lymphadenopathy and the high MECOM median expression level was significantly associated with lower hemoglobin concentrations at presentation. BAALC overexpression showed significant associations with the presence of CD34, the presence of wild type NPM1 mutation, and the absence of FLT3-ITD mutations. However, BAALC underexpression was significantly associated with normal cytogenetics, while its overexpression was associated with adverse and favorable cytogenetics, with a statistically significant difference between them (p = 0.049)*. Statistically significant positive correlation was found between BAALC expression levels and postinduction BM blast percentages. Among these two genes, only high BAALC expression had significantly shorter OS in AML patients based on the log rank test (p = 0.037)*.Conclusion BAALC expression might be a specific molecular marker used for the assessment of prognosis and OS in AML patients and might be used in the future as targeted therapy in AML, aiming to improve patient outcomes and OS.

Keywords

• AML
• NGS
• expression
• MECOM
• BAALC