Concise review: Defining and targeting myeloma stem cell-like cells

Area of Science:

• Hematology
• Oncology
• Cancer Stem Cell Biology

Background:

• Multiple myeloma (MM) remains an incurable hematologic malignancy despite therapeutic advances.
• The concept of MM cancer stem cells (CSCs) is implicated in drug resistance, but their precise definition and origin are debated.
• Distinct plasma cell populations in MM exhibit clonogenic potential, complicating the identification of MM-initiating cells.

Purpose of the Study:

• To clarify the definition and characteristics of multiple myeloma cancer stem cells (MM CSCs).
• To explore the dynamic nature and potential therapeutic targeting of MM CSCs.

Main Methods:

• Review and synthesis of existing literature on MM biology and CSCs.
• Analysis of phenotypic and functional heterogeneity within MM plasma cell populations.
• Discussion of potential therapeutic strategies targeting MM CSCs.

Main Results:

• MM CSCs are likely a dynamic, non-static population, interconverting between stem-like and non-stem-like states.
• Phenotypic heterogeneity exists within MM plasma cells, with some fractions possessing clonogenic capacity.
• MM CSCs exhibit distinct molecular, metabolic, and epigenetic signatures, along with self-renewal signaling.

Conclusions:

• MM CSCs represent a critical target for overcoming drug resistance in multiple myeloma.
• Understanding the plasticity and heterogeneity of MM CSCs is essential for developing effective therapies.
• Targeting the unique signatures and self-renewal pathways of MM CSCs holds clinical relevance for treating incurable MM.