Leukemia stem cell survival pathways (LSC survival pathways)

Leukemia stem cell (LSC) survival pathways represent a collection of signaling mechanisms and intrinsic regulatory circuits that enable a subpopulation of malignant cells to maintain self-renewal and resist therapy (Jordan, 2007, Nature). These pathways, including Wnt/beta-catenin, Hedgehog, and Notch, are often aberrantly activated in LSCs, providing them with the ability to remain quiescent and survive within the protective bone marrow microenvironment (Wang et al., 2017, Blood). Drugs such as Venetoclax, which targets the BCL-2 anti-apoptotic pathway, and Glasdegib, which inhibits the Hedgehog signaling component Smoothened, have been developed to specifically disrupt these survival signals (DiNardo et al., 2019, Journal of Clinical Oncology; Pollyea et al., 2018, Nature Reviews Clinical Oncology). By targeting these pathways, clinicians aim to eliminate the reservoir of cells responsible for disease relapse, although the overlap with normal hematopoietic stem cell (HSC) signaling poses significant risks for myelosuppression and other toxicities (Majeti, 2011, Hematology). Understanding the distinct metabolic and signaling requirements of LSCs compared to normal HSCs remains a primary focus for developing more selective and effective leukemia treatments.

Other names

Leukemia stem cell maintenance pathwaysLSC signaling pathwaysLeukemic stem cell self-renewal pathways

Inhibition of developmental signaling pathways (Hedgehog, Wnt, Notch), antagonism of anti-apoptotic proteins (BCL-2), and disruption of niche-mediated survival signals to induce exhaustion or apoptosis in the leukemic stem cell population.