title: Murine B-1 B cell progenitors initiate B-acute lymphoblastic leukemia with features of high-risk disease.
abstract: B-1 and B-2 B cells derive from distinct progenitors that emerge in overlapping waves of development. The number of murine B-1 progenitors peaks during fetal development whereas B-2 B cell production predominates in adult bone marrow. Many genetic mutations that underlie B-acute lymphoblastic leukemia (B-ALL) occur in the fetus, at which time B-1 progenitor numbers are high. However, whether B-ALL can initiate in B-1 progenitors is unknown. In the present study, we report that BCR-ABL-transformed murine B-1 progenitors can be B-ALL cells of origin and demonstrate that they initiate disease more rapidly than do oncogene-expressing B-2 progenitors. We further demonstrate that B-1 progenitors exhibit relative resistance to apoptosis and undergo significant growth following oncogene expression, and we propose that these properties underlie the accelerated kinetics with which they initiate leukemia. These results provide a developmental perspective on the origin of B-ALL and indicate B cell lineage as a factor influencing disease progression.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Encarnacion
authors.initials: E
authors.lastname: Montecino-Rodriguez
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Katy
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Michael
authors.initials: M
authors.lastname: Fice
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 kdorshki@mednet.ucla.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dorshkind
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000473:pathology
chemical_list: D016044:Fusion Proteins, bcr-abl
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