178 The Lymphocyte and Lymphocytic Tissue 



plasia, then we may expect a multicentric origin, secondary to a mobiliza- 

 tion of primitive mesenchymal cells. 



EXPERIMENTS ON THE GENESIS OF LEUKEMIA 



A series of experiments was undertaken to study the genesis of leukemia. 

 One group of animals received intracerebral injections and one group, intra- 

 peritoneal injections of leukemic cell-free liltrate from the brain; a third 

 group was injected with cell-free filtrate of brain from nonleukemic mice, 

 and a fourth group was injected intraperitoneal!) with tumor cells suspen- 

 sion. It was known that lymphoblastoma would develop in the animals a 

 week or two after inoculation; a number of animals from each group were 

 sacrificed each day. The tissues were studied as unknowns. Animals were 

 considered positive only when the diagnosis of lymphoblastoma could be 

 made unequivocally. 



We were particularly interested in ascertaining when and where the 

 earliest lymphomatous changes take place. We wished to know also whether 

 the leukemic transformation occurred in different areas sequentially or 

 simultaneously. We wanted to learn, further, whether the way the leukemia 

 develops differs when cell-free filtrates or tumor cells are used for purposes 

 of induction, or when intracerebral or intraperitoneal routes are used for 

 inoculation. 



Both C3H and Swiss mice were used. One tenth of a cubic centimeter 

 of the cell-free filtrates was used for the intracerebral and 0.5 cc, for the 

 intraperitoneal inoculation. In the tumor cell suspension experiments, 

 ()..") cc. of a tumor cell suspension containing approximately 10 ,J cells per 

 cubic centimeter was used. By the eighth day all the injected mice presented 

 gross evidence of leukemia. 



The fully manifest lymphoblastoma shows a complete obliteration and 

 replacement of lymph node architecture, tumor cell invasion of the peri- 

 nodal tissues, invasion of the salivary glands, and heavy infiltration of the 

 liver, kidneys, perirenal tissue, and genital organs. The skeletal muscles, 

 spleen, marrow, and central nervous system are inconstantly involved. The 

 progression of morphologic changes as observed at twenty-four hour in- 

 tervals was as follows. 



In twenty-four hours there were no specific changes. Some of the lymph 

 nodes show a nonspecific lymphadenitis. 



In forty-eight hours the earliest changes are seen in the fat tissue of the 

 mesentery, around the kidneys, and around the genital organs, where mono- 

 nuclear cells appear which resemble large lymphoblasts. These cells are 

 intermingled with polymorphonuclear leukocytes. The lymph nodes show 

 lymphadenitis. Such changes are not. seen in the animals inoculated 

 with nonleukemic brain filtrates. 



