title: Stem cell programs are retained in human leukemic lymphoblasts.
abstract: Leukemic lymphoblasts within different immunophenotypic populations possess stem cell properties. However, whether or not the self-renewal program is retained from stem cells or conferred on progenitors by leukemogenic molecules remains unknown. We have addressed the issue in the context of TEL-AML1-associated acute lymphoblastic leukemia (ALL) by profiling a refined program edited from genes essential for self-renewal of hematopoietic stem cells and B-cell development. Bioinformatic analysis shows that ALL populations are loosely clustered and close to the normal population that contains stem and primitive progenitor cells. This finding indicates that immunophenotypes do not reflect maturation stages in ALL and that the self-renewal program may be retained from stem cells. Results of assessing 'first hit' function of TEL-AML1 in different populations of normal cells demonstrate the molecular model. Therefore, the current study shows a leukemogenic scenario of human ALL in which programs of stem cells are sustained in distinct fractions by leukemogenic mutations.
authors.affiliation: Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Ruijin Hospital, SJTU-SM, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Ruijin Hospital, SJTU-SM, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Duan
authors.affiliation: Ruijin Hospital, SJTU-SM, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shanghai Cord Blood Bank, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Cord Blood Bank, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.affiliation: Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Enver
authors.affiliation: Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.affiliation: 1] Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China [2] Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Hong
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000293:Adolescent; D018941:Antigens, CD19 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D051997:ADP-ribosyl Cyclase 1; D018941:Antigens, CD19; D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein