title: Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1.
abstract: Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34⁺ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, Mexico ; Molecular Biomedicine Program, CINVESTAV, 07360 Mexico City, DF, Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Purizaca
authors.forename: Adriana
authors.initials: A
authors.lastname: Contreras-Quiroz
authors.forename: Elisa
authors.initials: E
authors.lastname: Dorantes-Acosta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vadillo
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.forename: Silvestre
authors.initials: S
authors.lastname: Fuentes-Figueroa
authors.forename: Horacio
authors.initials: H
authors.lastname: Villagomez-Barragán
authors.forename: Patricia
authors.initials: P
authors.lastname: Flores-Guzmán
authors.forename: Antonio
authors.initials: A
authors.lastname: Alvarado-Moreno
authors.forename: Hector
authors.initials: H
authors.lastname: Mayani
authors.forename: Isaura
authors.initials: I
authors.lastname: Meza
authors.forename: Rosaura
authors.initials: R
authors.lastname: Hernandez
authors.forename: Sara
authors.initials: S
authors.lastname: Huerta-Yepez
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D054503:Lymphoid Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D014157:Transcription Factors