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
Oncology Research Unit, Mexican Institute for Social Security, Mexico City, Mexico; Molecular Biomedicine Program, CINVESTAV, IPN, Mexico City, Mexico.
Oncology Research Unit, Mexican Institute for Social Security , Mexico City , Mexico.
Front Immunol. 2017 Jan 5;7:666. doi: 10.3389/fimmu.2016.00666. eCollection 2016.
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 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.
儿科肿瘤学，尤其是儿童急性淋巴细胞白血病（ALL），目前是全球主要的健康关注点之一，也是生物医学的重点领域。降低儿童白血病的总体死亡率需要全面了解其病理生物学。越来越清楚的是，恶性细胞与微环境之间的相互通讯以及控制早期细胞命运决定的微环境信号对肿瘤进展至关重要。我们在此表明，ALL骨髓（BM）的间充质基质细胞成分在许多功能特性上与其正常对应物不同，并且可能在白血病发展过程中起关键作用。增殖潜力降低，与产生促炎细胞因子的强大能力以及CXCL12和SCF的异常缺失形成对比，表明ALL BM中的白血病淋巴微环境是独特的，可能排除正常造血。三维共培养结构中的细胞能力测定表明白血病前体细胞具有生长优势，并且通过减少CXCL12具有微环境重塑能力，导致白血病细胞进展以牺牲正常微环境相关的淋巴细胞生成。
