Analysis of Normal Hematopoietic Stem and Progenitor Cell Contents in Childhood Acute Leukemia Bone Marrow
| Autor: | Alfonso Reyes-López, Antonio Sandoval-Cabrera, Armando Vilchis-Ordoñez, David Dozal, Hector Mayani, Juan Manuel Mejía-Aranguré, Eduardo Vadillo, Briceida López-Martínez, Juan Carlos Balandrán, Rosana Pelayo, Merle Denisse Laffont-Ortiz, Juan Carlos Núñez-Enríquez, Henry Quintela-Nuñez del Prado, Elva Jiménez-Hernández, Jessica L Prieto-Chávez |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Population Bone Marrow Cells Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 03 medical and health sciences 0302 clinical medicine Bone Marrow medicine Humans Progenitor cell education Child Acute leukemia education.field_of_study Stem Cells Cell Differentiation General Medicine medicine.disease Flow Cytometry Hematopoietic Stem Cells Coculture Techniques Haematopoiesis Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Bone marrow Stem cell |
| Zdroj: | Archives of medical research. 47(8) |
| ISSN: | 1873-5487 |
| Popis: | Background and Aims Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients. Methods Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established. Results Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut. Conclusions HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies. |
| Databáze: | OpenAIRE |
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