Frequent Clonal Evolution in Multiple Myeloma,

Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells. Various complex cytogenetic and molecular genetic aberrations are present that are important for prognostication and follow up investigation. We investigated the clonal evolution of multiple myeloma patients at relapse or at progression compared from the diagnosis by conventional cytogenetics, fluorescence in situ hybridization (FISH) and cytoplasmic immunoglobulin fluroscence in situ hybridization (cIg FISH). Methods: 35 patients diagnosed as multiple myeloma by bone marrow examination from January 2003 to March 2011 were included. Conventional cytogenetics were performed in all patients at diagnosis and at relapse or progression. FISH was performed in 24 patients with available specimen for at least 3 items including −13/del(13q), p53 deletion/del(17p), 1q21 gain, p16 deletion, IgH rearrangement, t(4;14) and t(14;16). The FISH results were confirmed with cytoplasmic immunoglobulin FISH specifically staining plasma cells. Results: Forty-nine percent of the patients had relapsed or progressed with additional clonal evolutions and they were detected by conventional cytogenetics. Numerical abnormalities were more frequent than structural abnormalities and structural abnormalities involving chromosome 1 was frequent. Thirty-five percent had developed −13/13q loss which is considered a poor prognostic factor. cIg-FISH found additional aberrations in 20% of the patients such as RB1 deletion, del(17p) and t(14;16). Conclusion: Conventional cytogenetics and cIG-FISH are both necessary in relapsed patient since clonal evolutions develop in many patients which may only be detected by one method. Full evaluation of cIg-FISH including non-poor prognostic factors may be considered since new clones evolve that can be a candidate of follow-up marker and since prognostic factors can change as treatment modality changes.

No relevant conflicts of interest to declare.