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AssigneeThe Trustees of the University of Pennsylvania
InventorsMariusz A. Wasik, Qian Zhang
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The invention provides methods of inhibiting epigenetic gene silencing in a cell expressing NPM/ALK or decreasing NPM/ALK content in a cell, by contacting a cell with an agent capable of increasing the concentration of Stat5a protein or its functional analog. Further, the invention provides a method of treating malignancies expressing oncogenic kinase by administering to a patient affected with a malignancy an agent capable of increasing the concentration of Stat5a protein or its epigenetically silenced functional tumor suppressor analog in a malignant cell. Finally, it provides a method to diagnose malignancy and monitor patient's response to therapy by analysis of the degree of DNA methylation of the gene encoding for Stat5a or its analog, their mRNA, or protein.
A method of inhibiting epigenetic gene silencing in a cell expressing NPM/ALK, another form of ALK, or another chimeric tyrosine kinase, comprising the step of contacting the cell or a subject with an effective amount of an agent capable of increasing the amount of Stat5a protein or its functional tumor suppressor analog in the cell.
A method of decreasing NPM/ALK, or another oncogenic-kinase content in a cell, comprising the step of contacting a cell expressing NPM/ALK or another oncogenic-kinase, with an effective amount of an agent capable of increasing the amount of Stat5a or its functional analog, thereby down-regulating the kinase gene expression in the cell.
A method of treating malignancies expressing chimeric tyrosine kinase in a subject, comprising the step of administering to the subject a composition comprising an agent capable of increasing the concentration of Stat5a protein or its functional tumor suppressor analog in the cell.
The method of claim 16, whereby the agent is Stat5a mRNA.
A method of treating malignancies expressing oncogenic kinase in a cell or subject, comprising the step of administering to the subject a composition comprising an agent capable of increasing the amount of Stat5a protein or its analog in the cell.
A method of preventing, inhibiting or suppressing epigenetic silencing of transcriptional expression of a tumor suppressor in a subject, comprising the step of contacting the subject with a therapeutically effective amount of a composition comprising an agent capable of inhibiting the expression or function of a transcription inhibitor, a Methylation binding domain protein, a DNMT or their combination.
A method of treating a T-cell lymphoma in a subject, comprising the step of administering to the subject a therapeutically effective amount of a composition comprising an agent capable of increasing the expression or function of Stat5a protein or its analog thereby treating T-cell lymphoma in the subject.
A method of inhibiting or suppressing a T-cell lymphoma in a subject, comprising the step of administering to the subject a therapeutically effective amount of a composition comprising an agent capable of increasing the expression or function of Stat5a protein or its analog thereby inhibiting or suppressing T-cell lymphoma in the subject.
A method of ameliorating symptoms associated with a T-cell lymphoma in a subject, comprising the step of administering to the subject a therapeutically effective amount of a composition comprising an agent capable of increasing the expression or function of Stat5a protein or its-analog thereby ameliorating symptoms associated with T-cell lymphoma in the subject.
The method of any one of claims 41-43, whereby the agent is capable of increasing Stat5a expression.
The method of claim 51, whereby the agent is Stat5a mRNA.
The method of claim 57, whereby the DNMT inhibitor is 5′-aza-2′-deoxy-cytidine (5′-aza).
A method of providing a diagnosis for the presence of a malignancy associated with expression of an oncogenic kinase in a subject, comprising the step of:
A method of providing a prognosis for the severity of a malignancy associated with expression of chimeric tyrosine kinase in a subject, comprising the step of:
A method of evaluating the effectiveness of a treatment regimen for a malignancy associated with expression of oncogenic kinase, comprising the step of:
The method of any one of claims 55, 56, 66 and 72, whereby the biological sample is a cell, a tissue, an organ, blood, sera, saliva, cerebrospinal fluid, plasma or their combination.
A method of providing a diagnosis for the presence of a malignancy associated with expression of oncogenic kinase, or evaluating a treatment effectiveness in a subject, comprising the step of:
Dependencies are inferred from the claim text.