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Clinical and Developmental Immunology
Volume 2013 (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

1Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, Mexico
2Molecular Biomedicine Program, CINVESTAV, 07360 Mexico City, DF, Mexico
3“Federico Gómez” Children’s Hospital, 06720 Mexico City, DF, Mexico
4Immunochemistry Research Unit, Medical Specialties Hospital, Mexican Institute for Social Security, 06720 Mexico City, DF, Mexico
5UMAE “Victorio de la Fuente Narváez”, 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

Received 18 May 2013; Revised 10 July 2013; Accepted 28 July 2013

Academic Editor: Niels Olsen Saraiva Camara

Copyright © 2013 Jessica Purizaca et al. This 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.

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.