Hematopoietic stem cells (HSCs) self-renew and primarily exist in a
glycolytic state during quiescence but switch to oxidative phosphorylation
(OXPHOS) upon differentiation. HSCs differentiate into multipotent progenitors
(MPPs), which lose the ability to self-renew but have increased frequency of
cell cycle progression and differentiation activity. The MPP then differentiates
to a common myeloid progenitor (CMP), which can become a
megakaryocyte–erythroid progenitor (MEP), generating erythrocytes and
platelets, or a granulocyte-macrophage progenitor (GMP), generating
granulocytes. Both HSCs, MPPs, and CMPs can potentially become a leukemic stem
cell (LSC) through the acquisition of transforming mutations. LSCs also have the
capacity for self-renewal and are uniquely reliant on OXPHOS. They differentiate
to produce leukemic blasts, which lose the ability to self-renew but can use
both glycolysis and OXPHOS. While leukemic blasts are sensitive to traditional
chemotherapy, LSCs require targeted therapies for their eradication. Created
with BioRender.com.