Biological and Clinical Implications of Clonal Heterogeneity and Clonal Evolution in Multiple Myeloma

Current Cancer Therapy Reviews
Giada Bianchi, Irene M Ghobrial

Abstract

Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in thi...Continue Reading

Citations

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Related Concepts

Bone Marrow
Malignant Neoplasms
Cell Survival
Drug Resistance
Biological Evolution
Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
Neoplasms
Plasma Cells
Disease Progression

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