Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human BCR-ABL positive and negative adult Acute Lymphoblastic Leukemia samples

ABSTRACT: A set of 37 BCR-ABL positive (21 and 16 of which expressed p185 and p210, respectively) and 17 BCR-ABL negative adult ALL specimens from MRC UKALLXII/ECOG E2993 intergroup study. Gene expression profiling was performed using the 3DNA Array 900 Expression Array Detection Kit (Genisphere, Hatfield, PA), according to the manufacturers instructions. Universal Human Reference RNA (Stratagene, La Jolla, CA) was used as a reference RNA. The results provide insights into molecular mechanisms and pathways associated with BCR-ABL oncogenesis.

ORGANISM(S): Homo sapiens

SUBMITTER: Janos Demeter

PROVIDER: E-SMDB-3750 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Differential gene expression patterns and interaction networks in BCR-ABL-positive and -negative adult acute lymphoblastic leukemias.

Juric Dejan D Lacayo Norman J NJ Ramsey Meghan C MC Racevskis Janis J Wiernik Peter H PH Rowe Jacob M JM Goldstone Anthony H AH O'Dwyer Peter J PJ Paietta Elisabeth E Sikic Branimir I BI

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20070220 11

<h4>Purpose</h4>To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL).<h4>Patients and methods</h4>DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL-positive, 16 p210BCR-ABL-positive and 17 BCR-ABL-negative specimens).<h4>Results</h4>Using supervised and unsupervised a ...[more]

PMID: 17312329

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Project description:Ubash3b, also known as suppressor of T-cell receptor signaling or Sts-1, is an ill-studied atypical tyrosine phosphatase with ubiquitin binding ability. In our previous study, we hypothesized that Ubash3b plays an inhibitory role in BCR-ABL signaling through binding and dephosphorylating BCR-ABL and its interactors. The Hantschel lab recently solved the crystal structures of the p210 PH and DH domains, which are absent in the p190 variant, and demonstrated that loss-of-function mutations in the PH domain altered BCR-ABL localization, thereby reducing the interaction between Ubash3b and p2104. Taken together, this suggests differential subcellular localization of Ubash3b as a mechanism by which it interacts more strongly with p201 as compared to p190. To better understand the global impact Ubash3b has on p210, its direct kinase substrates and proteins in its phosphotyrosine signaling network, we have taken an integrative approach by combining global phosphotyrosine profiling, proximity-dependent biotinylation (BioID) and total protein analysis to investigate p210 signaling upon Ubash3b knockdown (KD). The BioID system was used to characterize Ubash3b function in p210 signaling by examining its interactome. Importantly, in all of our BioID experiments, we employed a newly technique that we have recently developed, Biotinylation Site Identification Technology (BioSITe), which directly identifies biotinylated peptides thereby increasing the reliability of the identified interactors. Here, we additionally used short hairpin RNA (shRNA) interference and generated Ubash3b knock-down (KD) and non-targeting control shRNA lines in Ba/F3 BirA*-p210 cells. Ubash3b expression was reduced >90 % in the KD cells and had a substantial effect on global tyrosine phosphorylation and on the interactome of p210. Of the 1,421 unique tyrosine phosphorylation sites identified from 830 proteins, 379 sites (from 286 proteins) exhibited a substantial increase (ÃƒÂ¢Ã¢â‚¬Â°Ã‚Â¥2-fold) in tyrosine phosphorylation upon Ubash3b KD cells compared to control cells. To date, the interactome of Ubash3b has not been extensively investigated, however, some examination of Ubash3b in the context p210 signaling has been undertaken. We designed constructs of C-terminal BirA* tagged full length Ubash3b and a deletion mutant lacking the UBA and SH3 domains leaving only the phosphatase domain tethered to BirA*. A comparative analysis of the core interactors of p210 from previous studies and Ubash3b interactome from the current study revealed 36 proteins that interact with both p210 and Ubash3b.

Dataset Information

Transcription profiling of human BCR-ABL positive and negative adult Acute Lymphoblastic Leukemia samples

Publications

Differential gene expression patterns and interaction networks in BCR-ABL-positive and -negative adult acute lymphoblastic leukemias.

Similar Datasets

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