title: Leukemia propagating cells rebuild an evolving niche in response to therapy.
abstract: 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.
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Cai-Wen
authors.initials: CW
authors.lastname: Duan
authors.affiliation: Department of Hematology, Sixth People Hospital, SJTU-SM, Shanghai 200233, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology/Oncology and Department of Pathology, Shanghai Children's Medical Center, SJTU-SM, Shanghai 200127, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Hematology, Sixth People Hospital, SJTU-SM, Shanghai 200233, China.
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology/Oncology and Department of Pathology, Shanghai Children's Medical Center, SJTU-SM, Shanghai 200127, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Qin
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Xiang-Cheng
authors.initials: XC
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Cai
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Zuo-Qing
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology/Oncology and Department of Pathology, Shanghai Children's Medical Center, SJTU-SM, Shanghai 200127, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology/Oncology and Department of Pathology, Shanghai Children's Medical Center, SJTU-SM, Shanghai 200127, China.
authors.forename: Min-Zhi
authors.initials: MZ
authors.lastname: Yin
authors.affiliation: Department of Hematology, Sixth People Hospital, SJTU-SM, Shanghai 200233, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Shanghai Institute of Hematology, Ruijin Hospital, SJTU-SM, Shanghai 200025, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Mi
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Lin-Heng
authors.initials: LH
authors.lastname: Li
authors.affiliation: Stem Cell Laboratory, UCL Cancer Institute, University College London, London WC1E 6BT, UK. Electronic address: t.enver@ucl.ac.uk.
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. Electronic address: chengq@shsmu.edu.cn.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. Electronic address: dlhong@sjtu.edu.cn.
authors.forename: Deng-Li
authors.initials: DL
authors.lastname: Hong
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001706:Biopsy; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D003630:Daunorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055153:Stem Cell Niche / Q000187:drug effects*; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D003561:Cytarabine; D003630:Daunorubicin