Genomics and proteomics in multiple myeloma and Waldenström macroglobulinemia.

PURPOSE OF REVIEW

Multiple myeloma and Waldenström macroglobulinemia are incurable hematologic malignancies with similar clinical phenotypes characterized by over-production of monoclonal immunoglobulins. Translocations into the immunoglobulin heavy chain locus and aneuploidy are nearly universal in multiple myeloma, whereas Waldenström macroglobulinemia generally does not harbor translocations. Deletion of 6q is identified in 50% of patients with Waldenström macroglobulinemia, however. The genetic abnormalities in multiple myeloma and Waldenström macroglobulinemia have implications for disease progression, and the subsequent proteomic expression associated with each disease influences therapeutic decisions.

RECENT FINDINGS

Gene expression profiling in these hematologic malignancies demonstrated distinct differences in mRNA expression patterns. Following profiling, Waldenström macroglobulinemia samples clustered with chronic lymphocytic leukemia and normal B-cell samples. Profiling performed after separation of Waldenström macroglobulinemia samples into populations with plasma cell or B-cell morphology revealed that plasma cell Waldenström macroglobulinemia samples most closely resembled multiple myeloma samples rather than chronic lymphocytic leukemia or normal control samples.

SUMMARY

Diverse genetic abnormalities have been identified in these hematologic malignancies, although they have similar clinical features. Gene expression profiling has elucidated the impact of genetic abnormalities. Furthermore, it may be used to identify a specific pathway for therapeutic targeting, such as interleukin-6 in Waldenström macroglobulinemia.