Molecular control of cancer hallmarks by HH/GLI signaling in hematologic malignancies. (A) HH/GLI signaling in hematologic malignancies plays a key role in the establishment of cancer hallmarks. These illustrate the oncogenic mechanisms driven by HH/GLI in fluid cancers and represent common therapeutic vulnerabilities for the rational design of more effective and durable combination therapies. (B) Activation and intricate interactions between HH/GLI and other oncogenic driver pathways resulting in enhanced transforming activity through increased SMO-dependent and SMO-independent oncogenic GLI activation. (C) HH/GLI target genes and their association as causal factors in the establishment of cancer hallmarks determined by HH/GLI signaling (the color code of target gene clusters corresponds to the color code of cancer hallmarks in panel A).