Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6107457

Title:Bcr-Abl directed compositions and uses for inhibiting Philadelphia chromosome stimulated cell growth
Inventors:Arlinghaus, Ralph B.; Bellaire, TX, USA
Liu, Jiaxin; Bellaire, TX, USA
Lu, Dai; Houston, TX, USA
Lopez-Berestein, Gabriel; Bellaire, TX, USA
Summary:Described herein are peptide fragments of Bcr-Abl with tyrosine residues, methods of their phosphorylation, and applications thereof. The invention relates to methods by which bone marrow may be processed by the peptide and polypeptide compositions disclosed herein. Therapeutic applications of such compositions are included, such as in the enrichment of bone marrow stem cells for the detection of Philadelphia chromosome-negative cells prior to transplantation, especially as part of autologous bone marrow transplant therapy in the treatment of leukemia.
Abstract:Compositions comprising a mixture of peptides that bind to molecules involved in Bcr-Abl oncoprotein function are disclosed. In addition, expression of functional BCR protein (p160 BCR) or amino terminal fragments thereof (159, 221 and 413 amino terminal residues) by way of retrovirus vectors will oppose the biological function of Bcr-Abl (p160 BCR) or inactivate Bcr-Abl tyrosine kinase function or its signal transduction function. Bcr and Abl peptides, either tyrosine phosphorylated or unphosphorylated, that bind to a region near the amino terminus of Bcr to prevent formation of tetramer Bcr-Abl molecules, that bind to the SH2 domain of Grb2, to sites on tyrosine phosphorylated Shc protein, to sites of Crkl, and to an SH2 domain of Ras Gap comprise particular peptide preparations of the invention. The peptides and polypeptides inhibit Bcr-Abl oncoprotein activation, or block the oncogenic signal generated by the Bcr-Abl oncoprotein and, thereby, inhibit growth and induce cell death of leukemia cells expressing the oncoprotein. Methods for processing bone marrow using the peptide and polypeptide compositions of the invention are also provided. Stem cells present in bone marrow may thus be enriched for Philadelphia chromosome-negative cells prior to transplantation, particularly as part of autologous bone marrow transplant therapy of leukemia, including CML, ALL and AML.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6107457
Application Number:US1995000390353
Date Filed:16/02/1995
Date Published:22/08/2000
Assignee:Board of Regents, The University of Texas System, Austin, TX, USA

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