Acute myeloid leukemia blasts and leukemia stem cells (AML blasts and LSCs)

Acute myeloid leukemia (AML) blasts are immature, non-functional myeloid cells that accumulate in the bone marrow and blood, interfering with normal hematopoiesis (National Cancer Institute, 2023). Leukemia stem cells (LSCs) are a distinct, often quiescent subpopulation within the AML hierarchy that possesses self-renewal capacity and is responsible for disease initiation, maintenance, and frequent relapse after chemotherapy (Pollyea & Jordan, 2017, Blood). While traditional chemotherapy targets the rapidly dividing blasts, LSCs often survive due to their dormant state and specialized niche interactions, necessitating targeted therapies (Thomas & Majeti, 2017, Blood). Modern pharmacological approaches target specific molecular vulnerabilities within these cells, such as BCL-2 (targeted by venetoclax), FLT3 mutations (targeted by midostaurin), or surface antigens like CD33 (targeted by gemtuzumab ozogamicin) (DiNardo et al., 2019, NEJM). Eradicating the LSC population is considered essential for achieving long-term remission and potential cure in AML patients.

Other names

AML cellsMyeloblastsLeukemic progenitor cellsMalignant hematopoietic stem cellsAML LSCs

Therapeutic agents target these cells through various mechanisms: BCL-2 inhibition (e.g., venetoclax) induces apoptosis in oxidative phosphorylation-dependent LSCs (Lagadinou et al., 2013, Cell Stem Cell); antibody-drug conjugates (e.g., gemtuzumab ozogamicin) deliver cytotoxic payloads via CD33 endocytosis (Walter et al., 2012, Blood); and tyrosine kinase inhibitors (e.g., gilteritinib) block survival signaling in FLT3-mutated blasts (Perl et al., 2019, NEJM).