Recent Advances in Characterization of Pre-Leukemic/Leukemic Stem Cells in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease organized as a hierarchy similar to normal hematopoiesis. It is maintained and progresses by self-renewing leukemia stem cells (LSCs) that are usually quiescent and resistant to current chemotherapies and thus, contribute to leukemia relapse. Recently, more ancestral pre-leukemic hematopoietic stem cells (HSCs) were identified, suggesting that accumulation of mutations occurs in self-renewing HSCs. The pre-leukemic/leukemic stem cell model proposes that a non-genetic mechanism in leukemic process, harmonized together with the genetic model and recently identified epigenetic dysregulations, contributes to leukemia heterogeneity and treatment resistance. Here we review the recent advances in characterization of AML LSCs, identification of pre-leukemic HSCs, and emerging concept of cell origin that contributes to AML relapse. These profound insights into AML biology have clinical importance and great implications for future development of new anti-AML therapies.

Cell Mol Med Res. 2023;1(1):12-19
doi: https://doi.org/10.14740/cmmr18e