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ACGH analysis was performed in the spleen of βcat(ex3)osb mice

ABSTRACT: Cells of the osteoblast lineage affect homing, number of long term repopulating hematopoietic stem cells (HSCs) HSC mobilization and lineage determination and Blymphopoiesis . More recently osteoblasts were implicated in pre-leukemic conditions in mice. Yet, it has not been shown that a single genetic event taking place in osteoblastscan induce leukemogenesis. We show here that in mice, an activating mutation of β-catenin leading to development of acute myeloid leukemia (AML) with common chromosomal aberrationsand cell autonomous progression. Activated β-catenin stimulates expression of the Notch ligand Jagged-1 in osteoblasts. Subsequent activation of Notch signaling in HSCprogenitors induces the malignant changes. Demonstrating the pathogenetic role of theNotch pathway, genetic or pharmacological inhibition of Notch signaling ameliorates AML. Nuclear accumulation and increased β-catenin signaling in osteoblasts was also identified in 38% ofpatients with MDS/AML. These patients showed increased Notch signaling in hematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce AML, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeuticapproach to AML. The present entry describes a comparison of copy numbers of DNA from βcat(ex3)osb mice from the mouse spleen with that of WT (C57BL/J Mice) mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE51690 | GEO | 2014/01/21

SECONDARY ACCESSION(S): PRJNA224570

REPOSITORIES: GEO

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aCGH analysis was performed in the spleen of Î²cat(ex3)osb mice

Project description:Cells of the osteoblast lineage affect homing, number of long term repopulating hematopoietic stem cells (HSCs) HSC mobilization and lineage determination and Blymphopoiesis . More recently osteoblasts were implicated in pre-leukemic conditions in mice. Yet, it has not been shown that a single genetic event taking place in osteoblastscan induce leukemogenesis. We show here that in mice, an activating mutation of Î²-catenin leading to development of acute myeloid leukemia (AML) with common chromosomal aberrationsand cell autonomous progression. Activated Î²-catenin stimulates expression of the Notch ligand Jagged-1 in osteoblasts. Subsequent activation of Notch signaling in HSCprogenitors induces the malignant changes. Demonstrating the pathogenetic role of theNotch pathway, genetic or pharmacological inhibition of Notch signaling ameliorates AML. Nuclear accumulation and increased Î²-catenin signaling in osteoblasts was also identified in 38% ofpatients with MDS/AML. These patients showed increased Notch signaling in hematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce AML, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeuticapproach to AML. The present entry describes a comparison of copy numbers of DNA from Î²cat(ex3)osb mice from the mouse spleen with that of WT (C57BL/J Mice) mice. DNA from spleen myeloid cells from Î²cat(ex3)osb mice and WT mice were hybridized to Agilent CGH 244A arrays. DNA from spleen myeloid cells from Î²cat(ex3)osb mice in C57BL/J background was labeled with red dye. DNA from spleen myeloid cells from WT (C57BL/J) mice were labeled with green dye. There were five arrays with DNA from 1 mouse of each genotype per array.

2014-01-21 | E-GEOD-51690 | biostudies-arrayexpress

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Expression data from dermis of epithelial activated beta-catenin mutant mouse embryo

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Expression data from skin of epithelial activated beta-catenin mutant mouse embryo

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