title: BCR/ABL can promote CD19+cell growth but not render them long-term stemness.
abstract: BACKGROUND
  Cancer stem cells are a subpopulation of malignant cells that have the capacity of both self-renewal and reconstitution of the cancer. Eradication of cancer stem cells is crucial for curing the malignant disease. Previous studies in hematopoietic malignancies showed that leukemia stem cells (LSCs) in chronic myelogenous leukemia (CML) chronic phase are originated from a hematopoietic stem cell (HSC), while LSCs in acute myeloid leukemia (AML) can either be derived from HSCs or be transformed from myeloid progenitors. But in B-cell acute lymphoblastic leukemia (B-ALL), the origin of leukemia stem cells is not clear. In this study, we tested whether BCR/ABL could transform B-lineage committed CD19+cells to LSCs.
  
  
  METHODS
  The B-cell lymphoblastic leukemia mouse model was generated by transplanting BCR/ABL-containing retrovirus infected bone marrow (BM) cells or CD19+cells into recipient mice. In the secondary or tertiary transplantation experiment, the GFP+cells (leukemic cells) were isolated from primary or secondary B-ALL mice. In addition, the frequency of leukemia stem cells was determined by limited dilution assay.
  
  
  RESULTS
  We found that transducing BCR/ABL in CD19+cells can promote their colony formationin vitroand induce B-ALL like diseasein vivo. However, only BCR/ABL transduced whole BM cells can be transplanted multiple times in recipient mice, and the frequency of long-term LSCs from the latter ranges from 1/135 to 1/629.
  
  
  CONCLUSIONS
  These studies suggest that BCR/ABL is unable to confer the long-term stemness to committed B-lymphoid progenitors and imply that CD19 chimeric antigen receptor (CAR) modified T cell therapy may not be effective in eradicating LSCs in BCR/ABL+B-ALL.
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Donghe
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiao
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; ; Department of Biology, Brandeis University, Waltham, MA, USA.
authors.forename: Ruibao
authors.initials: R
authors.lastname: Ren
keywords: B-cell acute lymphoblastic leukemia (B-ALL); BCR/ABL; leukemia stem cell (LSC)