AUTHOR=Balandrán Juan Carlos , Purizaca Jessica , Enciso Jennifer , Dozal David , Sandoval Antonio , Jiménez-Hernández Elva , Alemán-Lazarini Leticia , Perez-Koldenkova Vadim , Quintela-Núñez del Prado Henry , Rios de los Ríos Jussara , Mayani Héctor , Ortiz-Navarrete Vianney , Guzman Monica L. , Pelayo Rosana TITLE=Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00666 DOI=10.3389/fimmu.2016.00666 ISSN=1664-3224 ABSTRACT=

Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis.