Tcl-1 gene and protein and related methods and compositions

Abstract

The present invention relates to nucleotide sequences of TCL-1 genes and amino acid sequences of their encoded proteins, as well as derivatives and analogs thereof, and antibodies thereto. The TCL-1 gene sequence is preferentially expressed early in T and B lymphocyte differentiation. The present invention further relates to the use of TCL-1 genes and their encoded proteins as diagnostic and therapeutic reagents for the detection and treatment of disease states associated with chromosomal abnormalities.

1 . A method of detecting a lymphoma that is associated with altered TCL-1 expression in a patient with lymphoma, comprising detecting the level of TCL-1 protein in a sample from the patient, wherein an increased level of TCL-1 protein in the sample, relative to the level of TCL-1 protein in a non-malignant sample, is indicative of a lymphoma that is associated with altered TCL-1 expression and identifies the patient as a candidate for a lymphoma therapy comprising the use of an inhibitor of TCL-1. 
     
     
         2 . The method of  claim 1 , wherein the patient has a chromosome 14 abnormality. 
     
     
         3 . The method of  claim 2 , wherein the chromosome 14 abnormality is selected from the group consisting of a t(14;14)(q11;q32) chromosome translocation, a inv(14)(q11;q32) chromosome inversion, a t(8;14) chromosome translocation, a t(14;18) chromosome translocation, and a t(8:22) chromosome translocation, or a combination thereof. 
     
     
         4 . The method of  claim 1 , wherein the lymphoma is a B-cell lymphoma. 
     
     
         5 . The method of  claim 4 , wherein the B-cell lymphoma is selected from the group consisting of an endemic Burkitt's lymphoma, a high-grade B-cell lymphoma, a B-cell lymphoma associated with ataxia-telangiectasia (AT) and a B-cell mantle cell lymphoma. 
     
     
         6 . The method of  claim 1 , wherein the lymphoma is a T-cell lymphoma. 
     
     
         7 . The method of  claim 6 , wherein the T-cell lymphoma is associated with ataxia-telangiectasia (AT). 
     
     
         8 . The method of  claim 1 , wherein the level of the TCL-1 protein in the sample is measured by an immunoassay. 
     
     
         9 . The method of  claim 8 , wherein the immunoassay is an enzyme linked immunosorbant assay (ELISA). 
     
     
         10 . The method of  claim 1 , wherein the level of the TCL-1 protein in the sample is measured by in situ hybridization. 
     
     
         11 . A method of detecting a leukemia that is associated with altered TCL-1 expression in a patient with leukemia, comprising detecting the level of TCL-1 protein in a sample from the patient, wherein an increased level of TCL-1 protein in the sample, relative to the level of TCL-1 protein in a non-malignant sample, is indicative of a leukemia that is associated with altered TCL-1 expression and identifies the patient as a candidate for a leukemia therapy comprising the use of an inhibitor of TCL-1. 
     
     
         12 . The method of  claim 11 , wherein the patient has a chromosome 14 abnormality. 
     
     
         13 . The method of  claim 12 , wherein the chromosome 14 abnormality is selected from the group consisting of a t(14;14)(q11;q32) chromosome translocation, a inv(14)(q11;q32) chromosome inversion, a t(8;14) chromosome translocation, a t(14;18) chromosome translocation, and a t(8:22) chromosome translocation, or a combination thereof. 
     
     
         14 . The method of  claim 11 , wherein the leukemia is a B-cell leukemia. 
     
     
         15 . The method of  claim 11 , wherein the B-cell leukemia is a B-cell leukemia associated with ataxia-telangiectasia (AT). 
     
     
         16 . The method of  claim 11 , wherein the leukemia is a T-cell leukemia. 
     
     
         17 . The method of  claim 16 , wherein the T-cell leukemia is selected from the group consisting of a T-prolymphocytic leukemia (T-PLL), a T-cell leukemia associated with ataxia-telangiectasia (AT), and an adult T-cell leukemia. 
     
     
         18 . The method of  claim 11 , wherein the level of the TCL-1 protein in the sample is measured by an immunoassay. 
     
     
         19 . The method of  claim 18 , wherein the immunoassay is an enzyme linked immunosorbant assay (ELISA). 
     
     
         20 . The method of  claim 11 , wherein the level of the TCL-1 protein in the sample is measured by in situ hybridization.