Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. 2008

Angela Colmone, and Maria Amorim, and Andrea L Pontier, and Sheng Wang, and Elizabeth Jablonski, and Dorothy A Sipkins
Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue MC 2115, Chicago, IL 60637, USA.

The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments that sequester transplanted human CD34+ (HPC-enriched) cells. CD34+ cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited CD34+ cell migration into malignant niches, normalized CD34+ cell numbers, and restored CD34+ cell mobilization in leukemic mice. These data suggest that the tumor microenvironment causes HPC dysfunction by usurping normal HPC niches and that therapeutic inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.

UI MeSH Term Description Entries
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006571 Heterocyclic Compounds Cyclic compounds that include atoms other than carbon in their ring structure. Heterocyclic Compound,Compound, Heterocyclic,Compounds, Heterocyclic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080027 Cyclams Compounds made of fourteen-member tetraamine macrocycles which bind strongly to a wide range of metal ions. 1,4,8,11-Tetraazacyclotetradecane,Bicyclams,Cyclam Derivatives,Cyclens,Tetraazamacrocycles,Derivatives, Cyclam
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001596 Benzylamines Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. Phenylmethylamine,alpha-Aminotoluene,alpha Aminotoluene

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