Unknown,Transcriptomics,Genomics,Proteomics

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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. DNA from spleen myeloid cells from βcat(ex3)osb mice and WT mice were hybridized to Agilent CGH 244A arrays. DNA from spleen myeloid cells from βcat(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.

ORGANISM(S): Mus musculus

SUBMITTER: Stavroula Kousteni 

PROVIDER: E-GEOD-51690 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cells of the osteoblast lineage affect the homing and the number of long-term repopulating haematopoietic stem cells, haematopoietic stem cell mobilization and lineage determination and B cell lymphopoiesis. Osteoblasts were recently implicated in pre-leukaemic conditions in mice. However, a single genetic change in osteoblasts that can induce leukaemogenesis has not been shown. Here we show that an activating mutation of β-catenin in mouse osteoblasts alters the differentiation potential of mye  ...[more]

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