Abstract: The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL, particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

Abstract: The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL, particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

Abstract: The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

Abstract: The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

Abstract: Methods and compositions for detecting a form of chronic lymphocytic leukemia in a subject are described which allow for distinguishing more aggressive forms of the disease from less aggressive forms. Particularly described methods include assaying a sample obtained from the subject having or suspected of having chronic lymphocytic leukemia for a marker selected from a vimentin cleavage product, annexin 5 and 6-phosphogluconolactonase. A combination of any of these markers may be assayed in particular embodiments of a method according to the present invention. In particular embodiments, detection of an intermediate weight vimentin cleavage product is indicative of a less aggressive form of CLL associated with good prognosis.

Abstract: Compositions comprising a purified, isolated antibody, humanized antibodies and precipitates directed against ROR-1, wherein the antibody binds ROR-1 with moderate to high affinity. The compositions may be used for detecting and isolating an amount of ROR-1 in a subject sample, and to evaluate the appearance, status, course, or treatment of a ROR-1 cancer in a subject. The ROR-1 antibodies are especially useful in identifying lymphomas and ademocarcinomas. Vaccines and related methods for protecting a subject against diseases that involve expression of ROR-1 are also provided.

Abstract: This invention relates to genes which encode accessory molecule ligands and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the accessory molecule ligands of this invention are also disclosed.

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF?, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF?, wherein the encoded domain or subdomain replaces a cleavage site of native TNF?, and a second nucleotide sequence encoding a domain or subdomain of native TNF? that binds to a TNF? receptor. The encoded chimeric TNF? is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF? receptor on the surface of a cell. The chimeric TNF? is therefore useful in methods for inducing apoptosis of a cell expressing a TNF? receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF? that is expressed on the surface of the cell.