Multiple myeloma cancer stem cells

Minjie Gao, Yuanyuan Kong, Guang Yang, Lu Gao and Jumei Shi _

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Oncotarget. 2016; 7:35466-35477. https://doi.org/10.18632/oncotarget.8154

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Minjie Gao1, Yuanyuan Kong1, Guang Yang1, Lu Gao1 and Jumei Shi1

1 Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

Correspondence to:

Jumei Shi, email:

Keywords: myeloma stem cells, surface marker, drug resistance, signaling pathways, microRNA

Received: December 14, 2015 Accepted: March 02, 2016 Published: March 17, 2016


Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment.

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