IG V-H GENE MUTATIONAL PATTERNS INDICATE DIFFERENT TUMOR-CELL STATUS IN HUMAN MYELOMA AND MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE

Plasma cell tumors display a wide spectrum of clinical progression, ra nging from aggressive multiple myeloma to a benign form known as monoc lonal gammopathy of undetermined significance (MGUS), which requires n o treatment. Because both diseases involve mature Ig-secreting plasma cells, the reason for this variation in malignant behavior is unclear. However, assessment of malignant potential is desirabie for choice of treatment protocols. Ig variable (V-H) gene sequence analysis has pre viously shown the tumor cell of multiple myeloma to be postfollicular, with mutated homogeneous clonal sequences indicating no continuing ex posure to the somatic hypermutation mechanism, and this was confirmed in 7 of 7 patients. Comparison of the V-H gene sequences in the monocl onal cells in MGUS yielded a different result, with 3 of 7 patients de monstrating mutated heterogeneous sequences consistent with the tumor cells remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM-positive precursor cell was identified that expresse d heterogeneous V-H sequences similar to those of the isotype-switched plasma cell. These results indicate that the clonal cells in MGUS dif fer from those in myeloma and suggest that the difference may reflect malignant potential. (C) 1996 by The American Society of Hematology.