title: In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties.
abstract: We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, 48129 Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: le Viseur
authors.forename: Marc
authors.initials: M
authors.lastname: Hotfilder
authors.forename: Simon
authors.initials: S
authors.lastname: Bomken
authors.forename: Kerrie
authors.initials: K
authors.lastname: Wilson
authors.forename: Silja
authors.initials: S
authors.lastname: Röttgers
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Annegret
authors.initials: A
authors.lastname: Rosemann
authors.forename: Julie
authors.initials: J
authors.lastname: Irving
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Stam
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Heribert
authors.initials: H
authors.lastname: Jürgens
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Josef
authors.initials: J
authors.lastname: Vormoor
mesh_terms: D000293:Adolescent; D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D018951:Antigens, CD20 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002675:Child, Preschool; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D018952:Antigens, CD34; D007136:Immunoglobulins