Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2013, Article ID 349067, 12 pages http://dx.doi.org/10.1155/2013/349067 Research Article Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 Jessica Purizaca, 1,2 Adriana Contreras-Quiroz, 1,2 Elisa Dorantes-Acosta, 3 Eduardo Vadillo, 1 Lourdes Arriaga-Pizano, 4 Silvestre Fuentes-Figueroa, 5 Horacio Villagomez-Barragán, 5 Patricia Flores-Guzmán, 1 Antonio Alvarado-Moreno, 6 Hector Mayani, 1 Isaura Meza, 2 Rosaura Hernandez, 2 Sara Huerta-Yepez, 3 and Rosana Pelayo 1 1 Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, Mexico 2 Molecular Biomedicine Program, CINVESTAV, 07360 Mexico City, DF, Mexico 3 “Federico G´ omez” Children’s Hospital, 06720 Mexico City, DF, Mexico 4 Immunochemistry Research Unit, Medical Specialties Hospital, Mexican Institute for Social Security, 06720 Mexico City, DF, Mexico 5 UMAE “Victorio de la Fuente Narv´ aez”, Mexican Institute for Social Security, 07760 Mexico City, DF, Mexico 6 “Carlos McGregor Sanchez” Hospital, Mexican Institute for Social Security, 03100 Mexico City, DF, Mexico Correspondence should be addressed to Rosana Pelayo; rosanapelayo@gmail.com Received 18 May 2013; Revised 10 July 2013; Accepted 28 July 2013 Academic Editor: Niels Olsen Saraiva Camara Copyright © 2013 Jessica Purizaca et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. Te aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage diferentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid diferentiation 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 purifed 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 Gf-1, which was highly expressed in primitive CD34 + cells. Together, our fndings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gf-1 expression in the regulation of the stem/progenitor cell biology is suggested. 1. Introduction Acute lymphoblastic leukemia (ALL), characterized by the malignant and uncontrolled proliferation of lymphoid pre- cursor cells within bone marrow (BM), is the hematological disorder with the highest frequency in childhood and the most common cause of mortality in children worldwide [1– 5]. Despite the relatively high disease control by therapeutic agents, relapses occur in approximately 20% of children due to minimal residual disease and a functional failure in the cancer surveillance mechanisms [6, 7]. Neither the precise origins of the leukemic cell, nor the biological behavior of the hematopoietic primitive cells in the leukemic setting are known. Moreover, the understanding of the mechanisms that damage the earliest steps of the lymphoid develop- mental program in ALL is incomplete, and the existence