Plasma cell disorders include a spectrum of premalignant conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), and the malignant counterpart, symptomatic multiple myeloma (MM). The initial transformation results in the establishment of a founder clone that is either hyperdiploid or nonhyperdiploid.1 This clone transits through premalignant phases, MGUS or SMM, acquiring additional genetic changes giving it the growth advantage before clinically manifesting in its malignant phase as MM. The genetic changes acquired over time establish multiple subclones giving growth advantages to different clones over time. Thus, the tumor could be dormant for quite some time until a mutation in a subclone gives a sudden burst of tumor growth resulting in symptomatic MM.
Munshi NC, Jagannath S, Avet-Loiseau H. Monoclonal Gammopathy May Be of Unpredictable Significance. JAMA Oncol. Published online July 18, 2019. doi:10.1001/jamaoncol.2019.1580
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