A vicious cycle of metabolic interaction between leukemia stem cells and adipose tissues: implications in cachexia and drug resistance

Compelling evidences from recent studies suggest that leukemia stem cells (LSCs), a small subpopulation of malignant cells with long-term self-renewal capacity, play a key role in leukemia development, drug resistance, and disease relapse and recurrence (1). It has also been known for some time that tumor microenvironment or tissue niches may exert profound effect on the fates and viability of LSCs. A recent study by Ye et al. revealed a metabolic interaction between LSCs and adipose tissues, and showed that LSCs could be segregated into two metabolically and functionally distinct subgroups by their expression of the fatty acid (FA) transporter CD36 (2). The authors also suggested that gonadal adipose tissue (GAT) might provide a preferred niche to support CD36⁺ LSCs and promote drug resistance in a mouse model of blast crisis chronic myeloid leukemia (CML).