PROLIFERATIVE DISEASES 



malignant proliferation of its progeny. Putnam regards the 

 second alternative as the most likely, primarily on the basis 

 of the chemical evidence of aberrant amino-acid composition 

 and arrangement. 



I hope it is not overstating the case to say that the multiple 

 myeloma findings provide the best possible material for 

 displaying the salient features of the clonal selection approach 

 to the phenomena of antibody production and of malignancy. 

 In most malignant conditions the cancer cells show little 

 overt evidence of functional abnormality apart from their 

 proliferative and destructive action. In a number of semi- 

 malignant tumours of endocrine organs hypersecretion of 

 the characteristic hormone may produce symptoms, but this 

 is usually no more than excessive liberation of a normal 

 product. In multiple myeloma, however, we are concerned 

 with a semi-malignant condition (a conditioned neoplasm) 

 arising from a cell stock which, according to the approach we 

 have been using, has been specifically evolved to produce 

 a multiplicity of protein patterns, by minor mutational 

 change. In the genesis of multiple myelomatosis, it is as- 

 sumed that a mutation results in a distortion of the naturally 

 labile globulin-synthesizing mechanism to produce an ab- 

 normal product. Concomitantly some aberration of control 

 which, again by hypothesis, is naturally a sensitive and labile 

 one, allows excessive proliferation in one particular environ- 

 ment, the bone marrow. Metastatic plasmacytomas elsewhere 

 are apparently rare and when they do occur they are found 

 mainly in the commonest sites of extramedullary blood 

 formation, spleen and liver. 



This characteristic of multiple myelomatosis, a free deter- 

 mination of proliferative lesions through the bone marrow to 

 the virtual exclusion of other tissues, has two important 

 implications : {a) that the aberrant cells are still under partial 

 control, that is, it represents a conditioned neoplasm, and 

 [b) it provides a strong support for the hypothesis that a 

 mesenchymal cell, after appropriate immunological stimula- 



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