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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2244.
Submitted July 24, 2002
Department of Medicine, Laboratory of Immune System Diseases and Oncology, CSIC Associated Unit, Alcala University, Madrid, Spain * Corresponding author; email: adelahera{at}cib.csic.es.
Circulating CD34+ cells are used in reparative medicine as a stem cell source, but they contain cells already committed to different lineages. Many think that B cell progenitors (BCP) are confined to bone marrow (BM) niches until they differentiate into B cells, and do not circulate in blood. The prevailing convention is that BCP transit a CD34+CD19--10+ early-B -> CD34+CD19+CD10+ B-cell progenitor (pro-B) -> CD34-CD19+CD10+ B-cell precursor (pre-B) differentiation pathway within BM. However, there are populations of CD34+CD10+ and CD34+CD19+ cells circulating in adult peripheral blood and neonatal umbilical cord blood (CB), that are operationally taken as BCP based on their phenotype although they have not been submitted to a systematic characterization of their gene expression profiles. Here, conventional CD34+CD19+CD10+ and novel CD34+CD19+CD10- BCP populations are characterized in CB by single-cell sorting and multiplex analyses of gene expression patterns. Circulating BCP are Pax-5+ cells that span the early-B, pro-B and pre-B developmental stages, defined by the profiles of rearranged V-D-JH, CD79, VpreB, recombination activating gene (RAG) and terminal deoxynucleotidyl transferase (TdT) expression. Contrary to the expectation, the circulating CD34+CD19-CD10+ cells are essentially devoid of Pax-5+ BCP. Interestingly, the novel CD34+CD19+CD10- BCP appears to be the normal counterpart of circulating pre-leukemic BCP that suffer chromosomal translocations in utero months or years before their promotion into infant acute lymphoblastic B-cell leukemia after secondary postnatal mutations. The results underline the power of single-cell analyses to characterize the gene expression profiles in minor population of rare cells, which has broad implications in biomedicine.
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