Multidrug-resistant leukemic cells (MDR leukemic cells)

Multidrug-resistant leukemic cells are malignant hematopoietic cells characterized by their ability to survive and proliferate despite exposure to diverse chemotherapeutic agents [1]. This multidrug resistance (MDR) phenotype is most commonly driven by the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (ABCB1), which actively pump cytotoxic drugs out of the cell, thereby preventing them from reaching their intracellular targets [2]. Beyond efflux pumps, these cells often exhibit secondary resistance mechanisms, including upregulated anti-apoptotic signaling (e.g., BCL-2), enhanced DNA repair capacity, and alterations in drug-target enzymes like topoisomerase II [3]. In clinical practice, the presence of MDR leukemic cells is a major cause of induction failure and relapse in patients with acute myeloid leukemia (AML) and other hematological malignancies [4]. Therapeutic efforts to target these cells involve using MDR inhibitors or reversal agents to block efflux transporters, though these have faced challenges in clinical trials due to off-target effects on healthy tissues and complex drug-drug interactions [5]. [1] Gottesman MM, et al. (2002) Nature Reviews Cancer; [2] Robey RW, et al. (2018) Nature Reviews Cancer; [3] Thomas H, Coley HM. (2003) Cancer Control; [4] Kelly RJ, et al. (2011) Therapeutic Advances in Hematology; [5] Shaffer BC, et al. (2012) Hematology/Oncology Clinics of North America.

Other names

MDR leukemiaChemoresistant leukemic cellsRefractory leukemic cellsP-gp positive leukemic cells

Inhibition of ATP-binding cassette (ABC) transporters to prevent drug efflux; modulation of apoptotic pathways; collateral sensitivity exploitation.