The role of Hedgehog signaling in hematologic malignancies

Hedgehog signaling has been implicated in certain hematologic malignancies. Chronic myelogenous leukemia (CML) stem cells are a subpopulation of CML cells responsible for propagating the disease. Hedgehog pathway upregulation can be detected in these cells, and growth of this cell population can be inhibited by naturally occurring Hedgehog pathway inhibitors.²¹

Another type of Hedgehog signaling, reverse paracrine, may play a role in other hematologic malignancies. In reverse paracrine signaling, tumors receive the Hedgehog ligand from stromal cells, which leads to Hedgehog pathway activation in the tumor cell and upregulation of tumor survival genes such as BCL2. Reverse paracrine signaling has been observed in hematologic models of B-cell lymphoma, multiple myeloma, and leukemia, in which Hedgehog secreted from the bone marrow stroma may be essential for survival of the tumor.^7,8