| http://purl.uniprot.org/citations/20522708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20522708 | http://www.w3.org/2000/01/rdf-schema#comment | "Targeted therapy with imatinib in chronic myeloid leukemia (CML) prompted a new treatment paradigm. Unlike CML, chronic lymphocytic leukemia (CLL) lacks an aberrant fusion protein kinase but instead displays increased phosphatidylinositol 3-kinase (PI3K) activity. To date, PI3K inhibitor development has been limited because of the requirement of this pathway for many essential cellular functions. Identification of the hematopoietic-selective isoform PI3K-δ unlocks a new therapeutic potential for B-cell malignancies. Herein, we demonstrate that PI3K has increased enzymatic activity and that PI3K-δ is expressed in CLL cells. A PI3K-δ selective inhibitor CAL-101 promoted apoptosis in primary CLL cells ex vivo in a dose- and time-dependent fashion that was independent of common prognostic markers. CAL-101-mediated cytotoxicity was caspase dependent and was not diminished by coculture on stromal cells. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell-activating factors CD40L, TNF-α, and fibronectin. In contrast to malignant cells, CAL-101 does not promote apoptosis in normal T cells or natural killer cells, nor does it diminish antibody-dependent cellular cytotoxicity. However, CAL-101 did decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2010-02-271171"xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Puri K.D."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Wei L."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Zhao W."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Jones J."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Flynn J.M."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Johnson A.J."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Byrd J.C."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Heerema N.A."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Lannutti B.J."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Wagner A.J."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Giese N.A."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Andritsos L."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Gordon A.L."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/author | "Herman S.E."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/pages | "2078-2088"xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/title | "Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals."xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://purl.uniprot.org/core/volume | "116"xsd:string |
| http://purl.uniprot.org/citations/20522708 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20522708 |
| http://purl.uniprot.org/citations/20522708 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20522708 |