Clonal Heterogeneity by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma: Enhanced Cytogenetic Risk Stratification

Abstract

Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells with the accumulation of malignant plasma cells in the bone marrow compartment. It accounts for approximately 1% of all malignant diseases, 10% of all hematological malignancies in whites and 20% in African Americans. Clinically, patients are characterized by excess bone marrow plasma cells, serum and /or urine monoclonal protein, osteolytic bony lesions, anemia, hypercalcemia and renal impairment. This disease is considered heterogenous both at the genetic level and in terms of clinical outcome. Chromosomal aberrations in MM are typically complex and represent a hallmark of the disease, involving many chromosomes that are altered both numerically and structurally. Among all prognostic factors described in MM, FISH abnormalities have been found to be the most predictive of outcomes. In addition to their prognostic value, there is some evidence that cytogenetic abnormalities may confer unique clinical and immunological disease characteristics, which may underlie their prognostic significance. Furthermore, poor outcomes associated with HR cytogenetic groups, have led to efforts to identify treatments and combinations with the potential to improve prognosis of patients with these abnormalities.