In pediatric lymphoblastic leukemia of B-cell origin, a small population of primitive blast cells is noncycling, suggesting them to be leukemia stem cell candidates.
Kinetic investigations in pediatric acute lymphoblastic leukemia (ALL) are based on all blast cells and, therefore, reflect the proliferative characteristics of the predominant immunophenotype of leukemic cells. Nothing is known about proliferation of immunologically defined rare subpopulations of leukemic cells. In this study, mononuclear cells from the bone marrow of 15 children with untreated CD19 B-cell precursor ALL were examined for proliferative features according to the immunophenotype. After exclusion of highly proliferating residual normal hematopoietic cells, ∼ 3% of blast cells were CD19 and showed a low percentage of cells in S-phase assessed by the bromodeoxyuridine labeling index (BrdU-LI): median BrdU-LI, 0.19% [interquartile range (IQR), 0.15-0.40%]. In contrast, a median BrdU-LI of 7.2% (IQR, 5.7-8.8%) was found for the major CD19 blast cell compartment. Staining smears of sorted CD19 cells for CD10 or CD34 revealed a small fraction of CD19CD10 or CD19CD34 blast cells. These cells were almost nonproliferating with a median BrdU-LI of <0.1% (IQR, 0-0.2%). This proliferative behavior is suggestive of a stem/progenitor cell function and, in addition, the low proliferative activity might render them more resistant to an antiproliferation-based chemotherapy. However, xenotransplantation experiments will be necessary to demonstrate a possible stem cell function.
Department of Pediatrics, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland. andreas.hirt@insel.ch
Andreas
A
Hirt
Anne-Marie
AM
Schmid
Roland A
RA
Ammann
Kurt
K
Leibundgut
D000293:Adolescent; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000503:physiopathology
D015703:Antigens, CD