title: Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis.
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 competenceex vivoassays 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.
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security, Mexico City, Mexico; Molecular Biomedicine Program, CINVESTAV, IPN, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Balandrán
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security , Mexico City , Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Purizaca
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security, Mexico City, Mexico; Biochemistry Sciences Program, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Enciso
authors.affiliation: Hospital para el Niño, Instituto Materno Infantil del Estado de México , Toluca , México.
authors.forename: David
authors.initials: D
authors.lastname: Dozal
authors.affiliation: Hospital para el Niño, Instituto Materno Infantil del Estado de México , Toluca , México.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sandoval
authors.affiliation: Servicio de Hematología, Hospital Pediátrico Moctezuma, SSA , Mexico City , Mexico.
authors.forename: Elva
authors.initials: E
authors.lastname: Jiménez-Hernández
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV , Mexico City , Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Alemán-Lazarini
authors.affiliation: Laboratorio de Microscopía, Centro de Instrumentos, Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , México.
authors.forename: Vadim
authors.initials: V
authors.lastname: Perez-Koldenkova
authors.affiliation: UMAE "Dr. Victorio de la Fuente Narvaez", Instituto Mexicano del Seguro Social , Mexico City , México.
authors.forename: Henry
authors.initials: H
authors.lastname: Quintela-Núñez Del Prado
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security, Mexico City, Mexico; Biochemistry Sciences Program, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
authors.forename: Jussara
authors.initials: J
authors.lastname: Rios de Los Ríos
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security , Mexico City , Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Mayani
authors.affiliation: Molecular Biomedicine Program, CINVESTAV, IPN , Mexico City , Mexico.
authors.forename: Vianney
authors.initials: V
authors.lastname: Ortiz-Navarrete
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medicine , New York, NY , USA.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Guzman
authors.affiliation: Oncology Research Unit, Mexican Institute for Social Security , Mexico City , Mexico.
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
keywords: CXCL12; acute lymphoblastic leukemia; leukemic niches; pro-inflammatory bone marrow; tumor microenvironment