Hematopoietic stem cells and leukemia cells (HSCs and LSCs)

Hematopoietic stem cells (HSCs) are multipotent cells primarily located in the bone marrow that are responsible for the lifelong production of all blood cell types through the process of hematopoiesis (NIH, 2021). Leukemia cells, particularly leukemic stem cells (LSCs), represent the malignant counterparts that have acquired genetic mutations allowing for uncontrolled self-renewal and a block in normal differentiation (Jordan et al., 2006). While HSCs are essential for maintaining a functional immune and circulatory system, LSCs drive the initiation, progression, and chemoresistance of various leukemias, such as Acute Myeloid Leukemia (AML). Therapeutic strategies in hematology aim to exploit molecular differences between these two populations, such as the expression of surface markers like CD123 or CD33, to selectively eliminate malignant cells while preserving the regenerative capacity of healthy HSCs (Majeti, 2011). Many current treatments, including intensive chemotherapy and targeted inhibitors like Venetoclax or Midostaurin, interact with these cells by inducing apoptosis or inhibiting critical survival signaling pathways (Druker et al., 2001). However, the close biological relationship between HSCs and LSCs often leads to significant treatment-related toxicities, most notably myelosuppression (Leukemia & Lymphoma Society, 2023).

Other names

Hematopoietic stem and progenitor cellsLeukemic stem cellsHSCsLSCsBlood-forming stem cellsMalignant hematopoiesis

Drugs targeting these cells act through various mechanisms including DNA intercalation (anthracyclines), antimetabolite action (cytarabine), inhibition of BCL-2 mediated anti-apoptotic signaling (venetoclax), and selective inhibition of mutated tyrosine kinases like BCR-ABL or FLT3 (NIH, 2023; Druker et al., 2001).