Dataset Information

Expression data from Sh2b3 Knock-out NOTCH1-induced leukemias

ABSTRACT: To formally address the tumor suppressor activity of Sh2b3 in vivo, we tested the interaction between oncogenic NOTCH1 and Sh2b3 loss in a retroviral- transduction bone marrow transplantation model of NOTCH-induced T-ALL Forced expression of activated NOTCH1 in this model typically results in full leukemia transformation 5-10 weeks later. We performed microarray gene expression analysis of Sh2b3 wild type and Sh2b3–/– NOTCH1 induced leukemias

OTHER RELATED OMICS DATASETS IN: PRJNA188332

ORGANISM(S): Mus musculus

SUBMITTER: Jacob M Rowe Kara Kelly Elisabeth Paietta Wendy K Chung Wei Tong Giuseppe Basso Michael Hadler Arianne Perez-Garcia Isaura Rigo Charles A LeDuc Adolfo A Ferrando Janis Racevskis Martin S Tallman Chaim Jalas Maddalena Paganin Alberto Ambesi-Impiombato

PROVIDER: E-GEOD-44025 | ArrayExpress | 2013-11-06

SECONDARY ACCESSION(S): GSE44025PRJNA188332

REPOSITORIES: GEO, ArrayExpress

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Publications

Genetic loss of SH2B3 in acute lymphoblastic leukemia.

Perez-Garcia Arianne A Ambesi-Impiombato Alberto A Hadler Michael M Rigo Isaura I LeDuc Charles A CA Kelly Kara K Jalas Chaim C Paietta Elisabeth E Racevskis Janis J Rowe Jacob M JM Tallman Martin S MS Paganin Maddalena M Basso Giuseppe G Tong Wei W Chung Wendy K WK Ferrando Adolfo A AA

Blood 20130801 14

The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription si ...[more]

PMID: 23908464

Similar Datasets

Project description:Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/?L, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.

			Action	DRS
	E-GEOD-44025.idf.txt	Idf
	E-GEOD-44025.processed.1.zip	Processed
	E-GEOD-44025.raw.1.zip	Raw
	E-GEOD-44025.sdrf.txt	Txt