Leukemic stem cells as a target for eliminating acute myeloid leukemia: Gaps in translational research

• Published in: Critical reviews in oncology/hematology Vol. 175; p. 103710
• Main Authors: Khaldoyanidi, Sophia K., Hindoyan, Antreas, Stein, Anthony, Subklewe, Marion
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022
• Subjects: Acute myeloid leukemia; Leukemic stem cells; Measurable residual disease; Measurable residual disease; Acute myeloid leukemia; Leukemic stem cells; acute myeloid leukemia; leukemic stem cells; measurable residual disease
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2022.103710

Relapse is common in acute myeloid leukemia (AML) and thought to be due to resistance of underlying leukemic stem cells (LSCs) to current standard therapies, although a lack of tools to measure the quantity and quality of these cells in patients precludes the clinical testing of this concept. This review discusses the current knowledge of LSC properties and appraises strategies aimed to bring the therapeutic targeting of LSCs to the bedside to improve patient outcomes. We highlight pathways and targets of interest and summarize available information on drugs that might eradicate LSCs. Future research is needed to close identified gaps in knowledge and provide evidence for the clinical efficacy of LSC-directed therapies to support the development of treatments that eliminate residual disease and prevent relapse, thereby increasing the cure rates of patients with AML. •AML relapse may be due to leukemic stem cell (LSC) resistance to standard therapies.•Lack of tools to quantify LSCs precludes clinical testing of their role in relapse.•LSC properties and strategies to target LSCs to improve outcomes are discussed.•LSC pathways and targets of interest are summarized and drugs of interest discussed.•Knowledge gaps remain; future LSC-directed therapies may improve AML cure rates.