Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia

We explored the roles of adenylyl cyclases (ADCYs) in acute myeloid leukemia (AML). Expression ADCYs in AML and their effect on prognosis was analyzed using data from Oncomine, GEPIA and cBioPortal databases. Frequently altered neighbor genes (FANGs) of ADCYs were detected using the 3D Genome Browser, after which the functions of these FANGs were predicted using Metascape tools. Cell viability and apoptosis were assessed using CCK-8 and Annexin V-FITC/PI kits. Expression levels of ADCYs were higher in AML cells lines and in bone marrow-derived mononuclear cells from AML patients than in control cells, and were predictive of a poor prognosis. A total of 58 ADCY FANGs were identified from the topologically associating domains on the basis of the Hi-C data. Functional analysis of these FANGs revealed abnormal activation of the MAPK signaling pathway. Drug sensitivity tests showed that fasudil plus trametinib or sapanisertib had a synergistic effect suppressing AML cell viability and increasing apoptosis. These findings suggest that dysregulation of ADCY expression leads to altered signaling in the MAPK pathway in AML and that the ADCY expression profile may be predictive of prognosis in AML patients.