Cancer Cell 25:778 (2014)
Leukemia Propagating Cells Rebuild an Evolving Niche in Response to Therapy.
Duan CW1, Shi J2, Chen J3, Wang B1, Yu YH2, Qin X3, Zhou XC1, Cai YJ1, Li ZQ1, Zhang F3, Yin MZ3, Tao Y2, Mi JQ4, Li LH5, Enver T6, Chen GQ7, Hong DL8.
Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a protective niche. We investigated patients' BM biopsies and found evidence of a similar process in patients receiving induction therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or function. We therefore identified a therapy-induced niche that protects CPCs.