Early Hematopoietic Differentiation in Acute Lymphoblastic Leukemia: The Interplay Between Leukemia-Initiating Cells and Abnormal Bone Marrow Microenvironment

Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis

“…Notably, in concordance with most types of cancer, induced chronic inflammation and editing of the microenvironment by tumoral cells have been reported in some hematological malignancies, including acute lymphoblastic leukemia (ALL) (2–5). …”

“…The hematopoietic microenvironment under homeostatic conditions is a highly organized complex and dynamic network of cells [including mesenchymal stromal cells (MSC), osteoblasts, adipocytes, endothelial cells, innate immune cells, etc.] and their natural products such as cytokines, chemokines, and extracellular matrix forming a supportive scaffold for hematopoiesis (4, 5). Based on their major non-hematopoietic cellular components, at least three distinct BM hematopoietic stem cell niches have been identified: the endosteal niche, shaped by osteoblasts lining the bone surface at the endosteum, the vascular niche formed with endothelial cells, and the perisinusoidal reticular niche built by a heterogeneous population of networking stromal cells with long processes and abundant expression of CXCL12 and leptin receptor (4, 15–17).…”

Reporte de la Primera Reunión Nacional de Consenso para la Inmunofenotipificación de Leucemias Agudas

“…1,2 Aunque las tasas de supervivencia han aumentado en los últimos años por el desarrollo de tratamientos eficientes, el diagnóstico tardío, la resistencia a la quimioterapia, la infiltración extramedular, la enfermedad residual y la recaída suelen empeorar significativamente el desenlace de la enfermedad, lo que subraya la necesidad de nuevas estrategias diagnósticas. 3 La producción oligoclonal descontrolada de células precursoras hematopoyéticas de la serie linfoide o mieloide en la médula ósea a expensas de su diferenciación normal es la característica principal de las leucemias agudas. 4 Entre ellas, la leucemia linfoblástica aguda (LLA) representa 23 % de los tumores malignos y 85 % de los casos de leucemia en población infantil, mientras que la leucemia mieloide aguda constituye 15 %.…”

Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks

“…Cancer is currently considered as a global child health priority (Gupta et al, 2014 ). The application of effective treatments to decrease overall childhood cancer mortality requires a comprehensive understanding of its origins and pathobiology, along with accurate diagnosis and early identification of high-risk groups (reviewed in Vilchis-Ordoñez et al, 2016 ). Strikingly, the clinical, molecular and biological heterogeneity of malignant diseases indicating an unsuspected multiclonal diversity has highlighted their complexity and the uncertainty of their cell population dynamics.…”

“…As suggested by our previous findings, ALL lymphoid precursors have the ability of responding to pathogen- or damage- associated molecular patterns via Toll-like receptor signaling by secreting soluble factors and altering their differentiation potentials (Dorantes-Acosta et al, 2013 ). The resulting pro-inflammatory microenvironment may expose them to prolonged proliferation, contributing tumor maintenance in a self-sustaining way while prompting the NF-κB-associated proliferation of normal progenitor cells (Vilchis-Ordoñez et al, 2015 , 2016 ). Some hematopoietic growth factors and pro-inflammatory cytokines, including granulocyte-colony stimulating factor (G-CSF), IFNα, IL-1α, IL-1β, IL-7, and TNFα were highly produced by ALL cells from a conspicuous group of patients co-expressing myeloid markers (Vilchis-Ordoñez et al, 2015 ).…”