Niche-directed therapy in acute myeloid leukemia: optimization of stem cell competition for niche occupancy

Abstract

Acute myeloid leukemia (AML) is an aggressive malignancy of stem cell origin that contributes to significant morbidity and mortality. The long-term prognosis remains dismal given the high likelihood for primary refractory or relapsed disease. An essential component of relapse is resurgence from the bone marrow. To date, the murine hematopoietic stem cell (HSC) niche has been clearly defined, but the human HSC niche is less well understood. The design of niche-based targeted therapies for AML must account for which cellular subsets compete for stem cell occupancy within respective bone marrow microenvironments. In this review, we highlight the principles of stem cell niche biology and discuss translational insights into the AML microenvironment as of 2021. Optimization of competition for niche occupancy is important for the elimination of measurable residual disease (MRD). Some of these novel therapeutics are in the pharmacologic pipeline for AML and may be especially useful in the setting of MRD.

Keywords:

• Acute myeloid leukemia
• bone marrow niche
• microenvironment
• targeted therapy
• hematopoietic stem cells

Disclosure statement

SAP serves on the AML Advisory Board for Bristol Myers Squibb and serves on the Multiple Myeloma Advisory Board for Pfizer. SAP reports a consultant role for the Dedham Group, Adivo Associates, and SIS International.

Additional information

Funding

TYZ is supported by National Cancer Institute (NCI) K08 Award: [1K08CA248940-01].