PROLIFERATIVE DISEASES 



later in life and showing the normal age incidence of malig- 

 nant disease. Features of interest from the point of view of 

 somatic mutation hypotheses are: 



(i) The fairly common termination of lymphoid follicular 

 reticulosis (Robb-Smith, 1947) in a lymphatic leukaemia. 

 This type of reticulosis is a relatively benign, initially focal 

 but slowly generalizing enlargement of lymph nodes due to 

 lymphoid hyperplasia in foUicular distribution. After years 

 it terminates by a more active process which is (a) the result 

 of involvement of increasing areas of bone marrow, or 

 {b) lymphatic leukaemia, or (c) development of malignant 

 invasive lymphoblastic sarcoma. Here we have a rather 

 clear indication of the supervention of one or other of two 

 mutations, each involving loss of one type of control. 



(ii) A greatly reduced capacity to produce antibody is 

 characteristic of chronic lymphatic leukaemia (Howell, 

 1920; Larson and Tomlinson, 1953) and throat infections 

 are a common initial symptom. This may mean no more than 

 a crowding out of all the elements concerned in normal anti- 

 body production. Equally it is compatible with the view 

 that the pathological lymphocytes present in overwhelming 

 majority represent only one, or a very few, clones, so that 

 capacity to react immunologically is greatly limited. An 

 observation in which a very high level of antibody of some 

 single type was associated with lymphatic leukaemia would 

 be the strongest possible evidence for a clonal hypothesis of 

 antibody production but, even if such exists, it would need 

 extreme good fortune to find the appropriate antigen. 



Of more importance is the common occurrence in lym- 

 phatic leukaemia of haemolytic anaemia with positive 

 Coombs test. According to Scott (1957), this is almost 

 a standard finding at some stage. Following Dacie (1954), 

 we regard the appearance of such auto-antibody as a result 

 of somatic mutation, something which might well be expected 

 to occur more frequently in the more actively repHcating cells 

 of lymphatic leukaemia than in normal lymphoblasts. It is 



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