Anaplastic Lymphoma Kinase (ALK) As An Oncogene Capable Of Transforming Normal Human Cells

Abstract

The present invention provides compositions and methods for transforming primary mammalian cells using an oncogenic form of ALK wherein the transformed cells display features of that of a corresponding tumor cell isolated from a cancer subject. The invention also provides a method for immortalizing normal CD4+ T lymphocytes with a lymphoma-characteristic form of ALK such as NPM-ALK.

1 . An isolated transformed mammalian cell, wherein the transformed cell is genetically modified to express an oncogenic anaplastic lymphoma kinase (ALK), and wherein the transformed cell exhibits one or more features of that of a corresponding tumor cell isolated from a cancer subject. 
     
     
         2 . The transformed cell of  claim 1 , wherein the oncogenic ALK is selected from the group consisting of NPM-ALK, EML4-ALK, RANBP-ALK, TPM3-ALK, TFG-ALK, KIF5B-ALK, ATIC-ALK, and CLTC-ALK. 
     
     
         3 . The transformed cell of  claim 1 , wherein the oncogenic ALK is a mutant carrying a mutation selected from the group consisting of R1275Q and F117L. 
     
     
         4 . The transformed cell of  claim 1 , wherein the cell is a T cell. 
     
     
         5 . The transformed cell of  claim 1 , wherein the cell exhibits one or more features of that of a corresponding tumor cell isolated from a cancer subject having anaplastic large-cell lymphoma (ALCL). 
     
     
         6 . The transformed cell of  claim 1 , wherein the cell exhibits one or more of perpetual cell growth, characteristic cell morphology, activation of the key signal transduction pathways and expression of CD30, IL-10 and PD-L1/CD274. 
     
     
         7 . The composition of  claim 1 , wherein the mammalian cell is a human cell and the subject is a human. 
     
     
         8 .- 13 . (canceled) 
     
     
         14 . An isolated immortalized cell produced by the method of claim  8 . 
     
     
         15 . A cell culture comprising the isolated cell of  claim 14 . 
     
     
         16 .- 18 . (canceled)