Fig. 1.

Stages of Multiple myeloma (MM) progression. The malignant transformation of B cells occurs through a stepwise process involving multiple genetic aberrations and interaction of the B cells with the BM microenvironment. MM evolves from being asymptomatic to symptomatic through acquisition of a fundamental genetic instability followed by further genetic and epigenetic changes to develop a diverse plasma cell clone with the oncogenic potential that enhances bone resorption process throughout the disease progression stages. MM progresses from MGUS (Monoclonal gammopathy of undetermined significance) to SMM (smoldering multiple myeloma) followed by medullary and extramedullary MM to plasma cell leukemia.