In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties.
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.
le Viseur
Christoph
C
Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, 48129 Münster, Germany.
Hotfilder
Marc
M
Bomken
Simon
S
Wilson
Kerrie
K
Röttgers
Silja
S
Schrauder
André
A
Rosemann
Annegret
A
Irving
Julie
J
Stam
Ronald W
RW
Shultz
Leonard D
LD
Harbott
Jochen
J
Jürgens
Heribert
H
Schrappe
Martin
M
Pieters
Rob
R
Vormoor
Josef
J
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
D018941:Antigens, CD19; D018951:Antigens, CD20; D018952:Antigens, CD34; D007136:Immunoglobulins