MULTIPLE MYELOMA 



the presence of abnormal protein in the plasma, and in many 

 instances the copious excretion in the urine of a small-molecu- 

 lar-weight protein with the unique physical quality of pre- 

 cipitation followed by re-solution on progressive heating. 

 There is often an excess of plasma cells in the circulating 

 blood. 



The most conspicuous feature of the blood changes is the 

 appearance in the electrophoresis diagram of an extremely 

 sharp peak indicating the presence of a high concentration 

 of a homogeneous protein species. It is of the highest impor- 

 tance for an interpretation that, although each individual 

 patient shows a single spike located at a constant position in the 

 electrophoretic pattern, the position varies widely from patient 

 to patient and may be virtually at any point in the globulin 

 range from cl^ to y^. The positions tend, however, to concen- 

 trate about the normal beta and gamma globulin peaks. In 

 most instances the abnormal protein is of the normal glo- 

 bulin molecular weight ( 1 60,000) but in a proportion of cases it 

 is of cryoglobulin or macroglobulin character. In amino-acid 

 composition, and in the nature of N-terminal amino acids, 

 we have the same sort of situation — a general resemblance 

 to normal gamma globulin and constant individual features 

 of difference in samples from the same patient, but specific 

 differences in structure from one patient to another. Exactly 

 the same expression could be used in regard to the antigenic 

 pattern of the abnormal proteins as tested with antisera 

 produced in rabbits. 



As Putnam points out, these findings pose a fundamental 

 problem. Is the abnormal protein one component of normal 

 serum being produced in abnormal amount or is it a qualita- 

 tively abnormal protein? It seems to be imphed in such a 

 question that the protein is being produced by a single type 

 of cell, a clone normally present which has been stimulated 

 to abnormal activity by some factor extrinsic to the cells 

 themselves, or a clone of intrinsic abnormality resulting from 

 somatic mutation of a normal cell and malignant or semi- 



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