Slow-replicating leukemia cells represent a leukemia stem cell population with high cell-surface CD74 expression.

Area of Science:

• Hematology
• Cancer Biology
• Stem Cell Research

Background:

• Quiescent leukemia stem cells (LSCs) persist post-treatment, leading to chemotherapy resistance and poor leukemia prognosis.
• Identifying these quiescent LSCs is crucial for developing effective eradication strategies.

Purpose of the Study:

• To identify and characterize quiescent leukemia stem cells (LSCs) in leukemia models.
• To investigate the role of CD74 as a potential surface marker for LSCs.

Main Methods:

• Utilized PKH26 cell-tracing dye to identify label-retaining, slow-cycling leukemia cells in vivo.
• Analyzed cell cycle phase (G0), colony formation, leukemia initiation potential, and chemo-resistance of PKH-retaining cells.
• Examined gene expression and cell surface marker profiles, focusing on CD74, in leukemia cells.

Main Results:

• Identified a slow-cycling, label-retaining leukemia cell population with enhanced colony formation and leukemia initiation potential.
• PKH-retaining cells exhibited higher chemo-resistance and preferential localization to the endosteal bone marrow.
• HLA class II histocompatibility antigen gamma chain (CD74) was highly expressed in these LSCs and on CD34+ human leukemia cells.
• CD74+ leukemia cells demonstrated increased stemness properties compared to CD74- cells.

Conclusions:

• The identified slow-cycling, PKH-retaining cells represent a leukemia stem cell (LSC) population.
• CD74 is a promising surface marker for LSCs, offering a potential target for leukemia therapy.