Stromal cell-mediated mitochondrial redox adaptation regulates drug resistance in childhood acute lymphoblastic leukemia.

ABSTRACT: Despite the high cure rates in childhood acute lymphoblastic leukemia (ALL), relapsed ALL remains a significant clinical problem. Genetic heterogeneity does not adequately explain variations in response to therapy. The chemoprotective tumor microenvironment may additionally contribute to disease recurrence. This study identifies metabolic reprogramming of leukemic cells by bone marrow stromal cells (BMSC) as a putative mechanism of drug resistance. In a BMSC-extracellular matrix culture model, BMSC produced chemoprotective soluble factors and facilitated the emergence of a reversible multidrug resistant phenotype in ALL cells. BMSC environment induced a mitochondrial calcium influx leading to increased reactive oxygen species (ROS) levels in ALL cells. In response to this oxidative stress,

SUBMITTER: Liu J 

PROVIDER: S-EPMC4767490 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature