While deregulated p16INK4A/CDK4/RB1 and p14ARF/MDM2/p53 axes are the most common hallmarks of MCL, several signaling pathways may be overactivated by the chronic activation of cytokine/interleukin (IL) receptors, and/or cell/cell or cell/extracellular matrix interactions promoted by an MCL-specific tumor microenvironment (TME). The gene discussed is CDKN2A; the disease is neoplasm.