From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells.

Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE

Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]

Cell Transformation, Neoplastic/*genetics ; Monoclonal Gammopathy of Undetermined Significance/*diagnosis ; Monoclonal Gammopathy of Undetermined Significance/*pathology ; Multiple Myeloma/*pathology ; Plasma Cells/*pathology ; Precancerous Conditions/*pathology; Bone Marrow/pathology ; Bone Marrow Cells/pathology ; Cell Transformation, Neoplastic/pathology ; Clonal Evolution/physiology ; DNA Copy Number Variations/genetics ; Disease Progression ; Humans ; Monoclonal Gammopathy of Undetermined Significance/genetics ; Multiple Myeloma/diagnosis ; Multiple Myeloma/genetics ; Mutation/genetics ; Tumor Microenvironment/physiology

Multiple myeloma (MM) is a treatable, but incurable, malignancy of plasma cells (PC) in the bone marrow (BM). It represents the final stage in a continuum of PC dyscrasias and is consistently preceded by a premalignant phase termed monoclonal gammopathy of undetermined significance (MGUS). The existence of this well-defined premalignant phase provides the opportunity to study clonal evolution of a premalignant condition into overt cancer. Unraveling the mechanisms of malignant transformation of PC could enable early identification of MGUS patients at high risk of progression and may point to novel therapeutic targets, thereby possibly delaying or preventing malignant transformation. The MGUS-to-MM progression requires multiple genomic events and the establishment of a permissive BM microenvironment, although it is generally not clear if the various microenvironmental events are causes or consequences of disease progression. Advances in gene-sequencing techniques and the use of serial paired analyses have allowed for a more specific identification of driver lesions. The challenge in cancer biology is to identify and target those lesions that confer selective advantage and thereby drive evolution of a premalignant clone. Here, we review recent advances in the understanding of malignant transformation of MGUS to MM. Cancer Res; 78(10); 2449-56. ©2018 AACR .
(©2018 American Association for Cancer Research.)

Date Created: 20180429 Date Completed: 20190612 Latest Revision: 20190613

20221213

10.1158/0008-5472.CAN-17-3115

29703720