Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of human bone marrow from acute myeloid leukemia patients and healthy donors.

ABSTRACT: AC133+ cell fractions were isolated from bone marrow of 33 acute myeloid leukemia patients and 10 healthy donors and their transcriptional profiles assessed with Affymetrix GeneChip Human Genome U133 Plus 2.0

ORGANISM(S): Homo sapiens

DISEASE(S): healthy donor

SUBMITTER: Alessandro Beghini

PROVIDER: E-MTAB-220 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Regeneration-associated WNT signaling is activated in long-term reconstituting AC133bright acute myeloid leukemia cells.

Beghini Alessandro A Corlazzoli Francesca F Del Giacco Luca L Re Matteo M Lazzaroni Francesca F Brioschi Matteo M Valentini Giorgio G Ferrazzi Fulvia F Ghilardi Anna A Righi Marco M Righi Marco M Turrini Mauro M Mignardi Marco M Cesana Clara C Bronte Vincenzo V Nilsson Mats M Morra Enrica E Cairoli Roberto R

Neoplasia (New York, N.Y.) 20121201 12

Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by two molecularly distinct self-renewing leukemic stem cell (LSC) populations most closely related to normal progenitors and organized as a hierarchy. A requirement for WNT/β-catenin signaling in the pathogenesis of AML has recently been suggested by a mouse model. However, its relationship to a specific molecular function promoting retention of self-renewing leukemia-initiating cells (LICs) in human remai ...[more]

PMID: 23308055

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Project description:Gene Expression analysis of a differentiation timeseries of human Mesenchymal Stem Cells (hMSCs) in the presence of adipogenic/osteogenic factors. hMSCs differentiate into fat cells when treated with dexamethasone (10^-6 M), insulin (10 ug/ml), rosiglitazone (10^-7 M) and IBMX (250 uM). TGFbeta (5 ng/ml) inhibits this process and redirects these cells to differentiate into bone cells. Introduction: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. Methods: In order be able to interfere with this process, we have investigated in vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted. By means of gene expression microarray analysis, we have investigated genes which are potential targets for prevention of fat cell differentiation. Results: Our data show that BMP2 promotes both adipogenic and osteogenic differentiation of hMSCs, while TGFÎ² inhibits differentiation into both lineages. However, when cells are cultured under adipogenic differentiation conditions, which contains cAMP-enhancing agents such as IBMX of PGE2, TGFÎ² promotes osteogenic differentiation, while at the same time inhibiting adipogenic differentiation. Gene expression and immunoblot analysis indicated that cAMP-induced suppression of HDAC5 levels plays an important role in the inhibitory effect of TGFÎ² on osteogenic differentiation. By means of gene expression microarray analysis, we have investigated genes which are downregulated by TGFÎ² under adipogenic differentiation conditions and may therefore be potential targets for prevention of fat cell differentiation. We thus identified 9 genes for which FDA-approved drugs are available. Our results show that drugs directed against the nuclear hormone receptor PPARG, the metalloproteinase ADAMTS5 and the aldo-keto reductase AKR1B10 inhibit adipogenic differentiation in a dose-dependent manner, although in contrast to TGFÎ² they do not appear to promote osteogenic differentiation. Conclusions: The approach chosen in this study has resulted in the identification of new targets for inhibition of fat cell differentiation, which may not only be relevant for prevention of osteoporosis, but also of obesity. hMSCs were induced to differentiate in the presence dexamethasone, insulin and rosiglitazone, to which was added either 50 ng/ml BMP2; BMP2 + TGFbeta; BMP2 + IBMX; BMP2 + TGFbeta + IBMX.

Dataset Information

Transcription profiling by array of human bone marrow from acute myeloid leukemia patients and healthy donors.

Publications

Regeneration-associated WNT signaling is activated in long-term reconstituting AC133bright acute myeloid leukemia cells.

Similar Datasets

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