In vivo animal model of human leukemia

Abstract

The present invention provides a process for making an in vivo model of human leukemia. The process includes the steps of: pre-conditioning an immunodeficient rodent by administering to the rodent a sub-lethal dose of irradiation and injecting the rodent with an effective pre-conditioning amount of human fetal cord blood mononuclear cells; maintaining the rodent for from about 5 to 10 days; and injecting the rodent with an effective engrafting amount of primary human leukemia cells. An in vivo and in vitro model of human leukemia are also provided.

1 . A process for making an in vivo model of human leukemia comprising: 
 a) pre-conditioning an immunodeficient rodent by administering to the rodent a sub-lethal dose of irradiation and injecting the rodent with an effective pre-conditioning amount of human hematopoietic stem cells;    b) maintaining the rodent from step (a) for from about 3 to about 12 days;    c) injecting the rodent from step (b) with an effective engrafting amount of primary human leukemia cells; and    d) allowing the primary human leukemia cells to engraft in the rodent to produce the in vivo model of human leukemia.    
   
   
       2 . The process of  claim 1  wherein the immunodeficient rodent is an immunodeficient mouse.  
   
   
       3 . The process of  claim 2  wherein the immunodeficient mouse is a NOD/scid mouse.  
   
   
       4 . The process of  claim 1  wherein administering the sub-lethal dose of irradiation is accomplished by irradiating the rodent with about 350 rads of total body gamma radiation.  
   
   
       5 . The process of  claim 1  wherein the effective engrafting amount of primary human leukemia cells is from about 10 6  to about 10 7  cells.  
   
   
       6 . The process of  claim 1  wherein the primary human leukemia cells are T-cell acute lymphoblastic leukemia (T-ALL) cells.  
   
   
       7 . The process of  claim 1  wherein the effective pre-conditioning amount of human hematopoietic stem cells is from about 10 6  to about 10 8  cells.  
   
   
       8 . (canceled)  
   
   
       9 . The process of  claim 1  wherein the human hematopoietic stem cells comprise mesenchymal stem cells.  
   
   
       10 . The in vivo model of human leukemia produced by the process of  claim 1 .  
   
   
       11 . An rodent comprising: human hematopoietic stem cells and engrafted human leukemia cells.  
   
   
       12 . The rodent of  claim 11  wherein the human leukemia[-initiating] cells are maintained within the rodent.  
   
   
       13 . The rodent of  claim 12  that is a mouse.  
   
   
       14 . The mouse of  claim 13  that is a NOD/scid mouse.  
   
   
       15 . The rodent of  claim 11  that is irradiated, injected with human hematopoietic stem cells, and then injected with human primary leukemia cells.  
   
   
       16 . The rodent of  claim 11  wherein the engrafted leukemia cells are found in the bone marrow and spleen of the rodent.  
   
   
       17 . (canceled)  
   
   
       18 . The process of  claim 1  wherein the human hematopoietic stem cells comprise bone marrow stem cells.  
   
   
       19 . The process of  claim 1  wherein the human hematopoietic stem cells comprise mononuclear cells.  
   
   
       20 . The process of  claim 19  wherein the mononuclear cells comprise human fetal cord blood mononuclear cells.  
   
   
       21 . The process of  claim 1  wherein the maintaining step is from 3 to 12 days.  
   
   
       22 . The process of  claim 1  wherein the maintaining step is from about 5 to about 10 days  
   
   
       23 . The process of  claim 1  wherein the maintaining step is from 5 to 10 days.