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BioMed Research International
Volume 2013 (2013), Article ID 846724, 13 pages
http://dx.doi.org/10.1155/2013/846724
Research Article

TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

1Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, Mexico
2Federico Gómez Children's Hospital, 06720 Mexico City, Mexico
3Medical Sciences Program, National Autonomous University of Mexico, 04510 Mexico City, Mexico
4National School of Biological Sciences, National Polytechnic Institute, 11340 Mexico City, Mexico
5Molecular Biomedicine Program, CINVESTAV, 07360 Mexico City, Mexico
6Immunochemistry Research Unit, Medical Specialties Hospital, Mexican Institute for Social Security, 06720 Mexico City, Mexico
7Moctezuma Children's Hospital, 15340 Mexico City, Mexico
8General Hospital, La Raza Medical Center, Mexican Institute for Social Security, 02990 Mexico City, Mexico

Received 1 May 2013; Accepted 22 July 2013

Academic Editor: Alessandro Isidori

Copyright © 2013 Elisa Dorantes-Acosta 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 leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs) in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.