title: Cytogenetically aberrant cells are present in the CD34+CD33-38-19- marrow compartment in children with acute lymphoblastic leukemia.
abstract: Acute lymphoblastic leukemia (ALL), the most common cancer in childhood, is characterized by clonal proliferation of transformed lymphoblasts that comprise the majority of marrow and/or blood specimens. Although the leukemic cells typically express antigens associated with lymphoid maturation or activation (ie CD19, CD38, etc), it has been suggested that ALL blasts may evolve from a more primitive precursor. Increased understanding of the phenotypic and molecular heterogeneity of cells in ALL may provide clues to leukemogenesis and/ or impact prognostication or treatment. We utilized a phenotype/genotype approach to measure the prevalence and frequency of cytogenetically aberrant cells in a phenotypically defined primitive compartment (CD34+33-19-38-; CD34+Lin-). Bone marrow cells were flow cytometrically sorted into CD34-Lin+, CD34+Lin+ and CD34+Lin- subpopulations. Fluorescence in situ hybridization (FISH) was used to quantify the frequency of cells with aneusomies in the sorted populations. Approximately 26% (5/19) of ALL cases at diagnosis contain cytogenetically aberrant CD34+Lin- cells. The frequency of cytogenetically aberrant cells in the CD34+Lin- compartment is independent of FAB, WBC and blast counts. These data indicate that cytogenetically aberrant cells may reside in a phenotypically defined primitive subpopulation and suggest that ALL blasts in some patients may evolve from a precursor compartment.
authors.affiliation: Department of Pediatrics, University of California, San Francisco 94115, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Quijano
authors.forename: D
authors.initials: D
authors.lastname: Moore
authors.forename: D
authors.initials: D
authors.lastname: Arthur
authors.forename: J
authors.initials: J
authors.lastname: Feusner
authors.forename: S S
authors.initials: SS
authors.lastname: Winter
authors.forename: M G
authors.initials: MG
authors.lastname: Pallavicini
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000782:Aneuploidy; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D008562:Membrane Glycoproteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1