Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of myeloma cells and accumulation of genetic lesions. MM progression is accompanied by increased aggressiveness and drug resistance. Even the goal of “cure” remains hard to reach for most patients, advances in diagnosis and treatment have allowed some to achieve durable remissions and transition to plateau phase. Single-cell sequencing, with its powerful ability to analyze cellular heterogeneity and molecular patterns at ground-breaking resolution, is informative for deciphering tumors and their microenvironment. In this review, we summarize the new insights of studies facilitated by emerging single-cell sequencing into clonal evolution, myeloma-supported microenvironment transformation, epigenetic changes, and novel prognostic and therapeutic strategies for MM, revealing the key mechanisms underlying MM progression and the direction of future efforts. With the continuous expansion of the research scope and optimization of related technologies, single-cell sequencing is expected to revolutionize our understanding of the biology and evolutionary dynamics of MM and contribute to the radical and precise improvement of treatment.