{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM1359549": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pre-B cells", "GENOTYPE": "wild type"}}, {"GSM1359549": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pre-B cells", "GENOTYPE": "wild type"}}, {"GSM1359549": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pre-B cells", "GENOTYPE": "wild type"}}, {"GSM1359552": {"STRAIN/BACKGROUND": "mixed 129/Sv and BALB/C", "CELL TYPE": "B-cell leukemia cells, arrested in pre-B-like stage", "GENOTYPE": "p53 -/-; Prkdc scid/scid double-mutant"}}, {"GSM1359552": {"STRAIN/BACKGROUND": "mixed 129/Sv and BALB/C", "CELL TYPE": "B-cell leukemia cells, arrested in pre-B-like stage", "GENOTYPE": "p53 -/-; Prkdc scid/scid double-mutant"}}, {"GSM1359552": {"STRAIN/BACKGROUND": "mixed 129/Sv and BALB/C", "CELL TYPE": "B-cell leukemia cells, arrested in pre-B-like stage", "GENOTYPE": "p53 -/-; Prkdc scid/scid double-mutant"}}, {"GSM1359555": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pro-B cells", "GENOTYPE": "wild type"}}, {"GSM1359555": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pro-B cells", "GENOTYPE": "wild type"}}, {"GSM1359555": {"STRAIN/BACKGROUND": "C57B/6", "CELL TYPE": "pro-B cells", "GENOTYPE": "wild type"}}], "id": 7601, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL. Intensified and central nervous system...", "geo_gse_id": "E-GEOD-56345", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 3, "sample_count": 9, "tags": ["acute lymphoblastic leukemia", "cell", "central", "disease", "leukemia", "liver", "lymphoblastic leukemia", "nervous system", "spleen", "tyrosine"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "therapeutic-potential-of-spleen-tyrosine-kinase-in", "geo_id_plat": "E-GEOD-56345_A-AFFY-45", "name": "Therapeutic potential of spleen tyrosine kinase inhibition for treatment of high-risk precursor B-cell acute lymphoblastic leukemia", "created": "Nov.12, 2014", "summary": "This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL. Intensified and central nervous system (CNS)-directed chemotherapy has significantly improved outcomes for pediatric B-acute lymphoblastic leukemia (B-ALL), but confers significant late-effect morbidities. Moreover, many patients suffer relapses, underscoring the need to develop novel, molecularly targeted B-ALL therapies. Using a mouse model, we showed that leukemic B-cells require pre-B-cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) signaling in vivo. In diagnostic samples from human B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated growth of 69 B-ALL samples, including high-risk (HR) subtypes. Orally administered fostamatinib significantly reduced high disease burden after xenotransplantation of HR B-ALL samples into immune-deficient mice, and decreased leukemia dissemination into spleen, liver, kidneys and the CNS of recipients. Thus, SYK activation sustains growth of multiple HR B-ALL subtypes, suggesting that SYK inhibitors may improve outcomes for HR and relapsed B-ALL. B-cell leukemia samples (3) from a mutant mouse model were compared to sorted or cultured preB or proB cells from normal mice using Affymetrix GeneChip arrays.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-56345", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-56345/samples/"}