The RAS pathway in CMML: recurrent mutations and therapeutic approaches. Activating and inactivating mutations are indicated by green and red stars, respectively. Mutations most commonly dominant are indicated in navy bubbles; those mostly subclonal are in pink bubbles. Selected therapeutic agents and their targets are showcased: those considered to have failed clinical development are in red text; those currently in clinical trials that include patients with CMML are in green text; agents with potential promise for repurposing to RAS-mutated CMML are in blue text. GDP, guanosine diphosphate; GM-CSF, granulocyte-macrophage colony-stimulating factor.