HUMAN LEUKAEMIA 



implied in this that the producers of abnormal antibody are 

 in the same line of descent as the small lymphocytes of 

 lymphatic leukaemia. Another closely related point is the 

 frequent association of abnormal globulins, cryoglobulin or 

 macroglobulin, with lymphatic leukaemia. If, as has been 

 suggested (Mackay, 1956) the presence (in abnormally 

 high proportion) of macroglobulin in the serum is due to 

 a mutation associated with proliferation of the clone of the 

 cell concerned, this would indicate that the cells producing 

 macroglobulins, and perhaps gamma globulins generally, 

 are also on the lymphocytic line of descent. 



(iii) Although the condition is essentially one of the acute 

 leukaemias of childhood, acute sarcoma-cell leukaemia may be 

 mentioned in which a sarcomatous process in lymph nodes, 

 usually mediastinal, is associated with lymphoblastic cells 

 in large number in the blood. Here we have a combination 

 of two releases from control, one allowing tissue invasion, the 

 other massive release into the blood stream. 



The final point of interest in relation to chronic lymphatic 

 leukaemia is why a condition which is clearly not 'fully 

 malignant' should show the typical cancer age incidence. 

 This impUes, in our view, that the diagnosable condition is 

 a result of two or more consecutive mutational steps, at least 

 one of which (before the final mutation) is associated with 

 prohferative advantage. This would suggest that there may 

 be undemonstrable mutations going on through life which 

 would give some clones a marked survival advantage, pre- 

 sumably with an associated elimination of other clones. This 

 might be expected to result on the clonal selection hypothesis 

 of a diminishing ability to react to any new antigen in old age. 

 The expectation may perhaps have been realized in Sabin 

 et al.'s (1947) finding that elderly Japanese failed to respond 

 to Japanese B virus vaccine unless they had some evidence of 

 previous contact with the virus. There are possibilities here 

 of useful work with a better-defined series of antigens. 



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