Leukemia stem cell (LSC) (LSC)

Leukemia stem cells (LSCs) are a distinct subpopulation of malignant cells characterized by their ability to self-renew and differentiate into the heterogeneous blast cells that define leukemia [Bonnet and Dick, Nature Medicine 1997]. These cells are often quiescent, residing in the G0 phase of the cell cycle, which allows them to survive conventional chemotherapy that targets rapidly proliferating cells [Thomas and Majeti, Blood 2017]. LSCs are primarily found within specialized niches in the bone marrow, where they receive protective signals from the microenvironment that promote drug resistance and survival [Pollyea et al., Nature Medicine 2018]. They are identified by specific immunophenotypes, most commonly CD34+/CD38- in acute myeloid leukemia, along with the expression of markers like CD123 and TIM-3 [Jordan et al., Leukemia 2000]. Because LSCs are responsible for disease initiation, maintenance, and relapse, they are a primary focus for novel therapeutic strategies. Current pharmacological approaches include the use of BCL-2 inhibitors to disrupt their unique metabolic dependencies and Hedgehog pathway inhibitors to impair their self-renewal capacity [Cortes et al., Leukemia 2019]. Eradicating this population is considered a prerequisite for achieving a permanent cure in leukemic patients.

Other names

Leukemic stem cellsLeukemia-initiating cellsLICsAML stem cells

Therapeutic agents target leukemia stem cells through various mechanisms, including the inhibition of anti-apoptotic proteins like BCL-2 to disrupt oxidative phosphorylation, blockade of developmental pathways such as Hedgehog or Wnt/beta-catenin, and direct targeting of surface antigens via antibody-drug conjugates or CAR-T cells [Thomas and Majeti, Blood 2017; Pollyea et al., Nature Medicine 2018].