Pathology and treatment of multiple myeloma understood from the tumor cell-of-origin perspective

Abstract

The treatment paradigm in multiple myeloma (MM) together with the introduction of novel agents have resulted in a considerably improved survival. However, the disease is still considered incurable. One of the factors of its recurrence was that acquired genomic events associated with the progression of MM lead to inter- and intrapatient clonal heterogeneities. Also, just like many other cancers, MM contains cancer stem cells, a rare subpopulation of MM cells that exhibit the capacity for self-renewal and differentiation, but also pronounced drug resistance. Furthermore, a growing body of evidence suggests the role of tumor microenvironment and anti-myeloma immune status in the progression and maintenance of MM. Despite much progress in MM pathology, there are still several issues left unsolved. In this review, we will discuss the recent advances in our understanding of the pathology of MM from the perspective of tumor cell-of-origin and how these advances can lead to more effective therapies targeting MM.